Open Access Articles- Top Results for Methylphenidate


"Concerta" redirects here. For the musical composition, see Concerto.

Systematic (IUPAC) name
methyl 2-phenyl-2-(piperidin-2-yl)acetate
Clinical data
Trade names Concerta, Methylin, Ritalin, Medikinet, Equasym XL, Quillivant XR, Metadate
AHFS/ monograph
MedlinePlus a682188
Licence data US FDA:link
  • AU: B3
  • US: C (Risk not ruled out)
Physical: None
Psychological: Moderate
Oral, insufflation, intravenous, transdermal
Pharmacokinetic data
Bioavailability ~30% (range: 11–52%)
Protein binding 10–33%
Metabolism Liver (80%)
Half-life 2–3 hours [1]
Excretion Urine (90%)
113-45-1 7pxY
PubChem CID 4158
DrugBank DB00422 7pxY
ChemSpider 4015 7pxY
UNII 207ZZ9QZ49 7pxY
KEGG D04999 7pxY
ChEBI CHEBI:6887 7pxY
Chemical data
Formula C14H19NO2
233.31 g/mol
Physical data
Melting point Script error: No such module "convert". [2]
Boiling point Script error: No such module "convert". [2]
 14pxY (what is this?)  (verify)

Methylphenidate (trade names Concerta, Methylin, Medikinet, Ritalin, Equasym XL, Quillivant XR, Metadate) is a central nervous system (CNS) stimulant of the phenethylamine[3] and piperidine classes that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Methylphenidate has been studied and researched for over 50 years and has a very good efficacy and safety record for the treatment of ADHD.[4] The original patent was owned by CIBA, now Novartis Corporation. It was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating what was then known as hyperactivity.

Prescribed to patients beginning in 1960, the drug has become increasingly heavily prescribed since the 1990s, when the diagnosis of ADHD itself became more widely accepted.[5][6] Between 2007 and 2012 methylphenidate prescriptions increased by 50% in Britain and in 2013 global methylphenidate consumption increased to 2.4 billion doses, a 66% increase compared to the year before. The US continues to account for more than 80% of global consumption.[7][8] While some people[who?] fear that methylphenidate is being over-prescribed without enough research into its harmful effects, others[who?] see it as a useful medication for relieving ADHD with few side effects.[citation needed]

ADHD and other similar conditions are believed to be linked to sub-performance of the dopamine and norepinephrine functions in the brain, primarily in the prefrontal cortex, responsible for self-regulatory function (e.g., inhibition, motivation, and memory) and executive function (e.g., reasoning, organizing, problem solving, and planning).[9][10] Methylphenidate's mechanism of action involves the inhibition of catecholamine reuptake, primarily as a dopamine reuptake inhibitor. Methylphenidate acts by blocking the dopamine transporter and norepinephrine transporter, leading to increased concentrations of dopamine and norepinephrine within the synaptic cleft. This effect in turn leads to increased neurotransmission of dopamine and norepinephrine. Methylphenidate is also a 5HT1A receptor agonist.[11]



MPH is a commonly prescribed psychostimulant and works by increasing the activity of the central nervous system.[12] It produces such effects as increasing or maintaining alertness, combating fatigue, and improving attention.[13] The short-term benefits and cost effectiveness of methylphenidate are well established.[14][15] Methylphenidate is not approved for children under six years of age.[16][17] Methylphenidate may also be prescribed for off-label use in treatment-resistant cases of bipolar disorder and major depressive disorder.[18]

Long-term effects

Meta-analyses and systematic reviews of magnetic resonance imaging studies suggest that long-term treatment with ADHD stimulants (specifically, amphetamine and methylphenidate) decreases abnormalities in brain structure and function found in subjects with ADHD.[19][20][21] Moreover, reviews of clinical stimulant research have established the safety and effectiveness of the long-term use of ADHD stimulants for individuals with ADHD.[22][23] In particular, the continuous treatment effectiveness and safety of both amphetamine and methylphenidate have been demonstrated in controlled drug trials with durations of several years.[23][24]

Attention deficit hyperactivity disorder

Methylphenidate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder.[25] The addition of behavioural modification therapy (e.g. cognitive behavioral therapy (CBT)) has additional benefits on treatment outcome.[26][27] People with ADHD have an increased risk of substance abuse, and stimulant medications reduce this risk.[28][29] A 2010 study on methylphenidate for adult ADHD suggested that methylphenidate doesn't have the previously expected effect of improving long-term academic outcomes in these individuals.[30]

The dosage used can vary quite significantly among individuals with some people responding to quite low doses, whereas others require a higher dose range; consequently, dosage should be titrated to an optimal level that achieves therapeutic benefit and minimal side-effects.[31]

Mechanisms of ADHD
Main article: ADHD

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems,[note 1] particularly those involving dopamine and norepinephrine.[32] Psychostimulants like methylphenidate and amphetamine may be effective in treating ADHD because they increase neurotransmitter activity in these systems.[32] Approximately 70% of those who use these stimulants see improvements in ADHD symptoms.[33][34] Children with ADHD who use stimulant medications generally have better relationships with peers and family members,[22][33] generally perform better in school, are less distractible and impulsive, and have longer attention spans.[22][33]

Studies confirm that biological and genetic differences of the kinds predicted by low arousal theory are clearly visible in ADHD individuals[citation needed], and have been confirmed both genetically and by in vivo scans of ADHD affected brains. MRI scans have revealed that people with ADHD show differences from non-ADHD individuals in brain regions important for attention regulation and control of impulsive behavior.[35] Methylphenidate's cognitive enhancement effects have been investigated using fMRI scans even in non-ADHD brains, which revealed modulation of brain activity in ways that enhance mental focus.[citation needed] Methylphenidate increases activity in the prefrontal cortex and attention-related areas of the parietal cortex during challenging mental tasks. Methylphenidate also increased deactivation of default network regions during the task.[36]

Aggression and criminality

Two studies state that methylphenidate is indicated for the treatment of ADHD in adults with a history of aggressive and criminal behavior. A large clinical study conducted in Sweden found a significant reduction of the criminality rate in males (32%) and females (42%) as compared with the rate for the same patients while not receiving medication.[37] Some of these clinical outcomes have been confirmed in similar studies with children and adolescents.[38]


Narcolepsy, a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden need for sleep, is treated primarily with stimulants. Methylphenidate is considered effective in increasing wakefulness, vigilance, and performance.[39] Methylphenidate improves measures of somnolence on standardized tests, such as the Multiple Sleep Latency Test, but performance does not improve to levels comparable to healthy controls.[40]


Use of stimulants such as methylphenidate in cases of treatment-resistant depression is controversial.[41] In individuals with cancer, methylphenidate is commonly used to counteract opioid-induced somnolence, to increase the analgesic effects of opioids, to treat depression, and to improve cognitive function.[42] Methylphenidate may be used in addition to an antidepressant for refractory major depressive disorder. It can also improve depression in several groups including stroke, cancer, and HIV-positive patients.[43] However, benefits tend to be only partial with stimulants.[citation needed] Stimulants may, however, have fewer side-effects than tricyclic antidepressants in the elderly and medically ill.[44]


A 2015 meta-analysis of high quality evidence found that therapeutic doses of amphetamine and methylphenidate result in modest improvements in performance on working memory, episodic memory, and inhibitory control tests in normal healthy adults.[45] Methylphenidate and other ADHD stimulants also improve task saliency and increase arousal.[46][47] Stimulants such as amphetamine and methylphenidate can improve performance on difficult and boring tasks,[46][47] and are used by some students as a study and test-taking aid.[48] Based upon studies of self-reported illicit stimulant use, performance-enhancing use, rather than use as a recreational drug, is the primary reason that students use stimulants.[49] Excessive doses of methylphenidate, above the therapeutic range, can interfere with working memory and cognitive control.[46][47] Like amphetamine and bupropion, methylphenidate increases stamina and endurance in humans primarily through reuptake inhibition of dopamine in the central nervous system.[50] Similar to the loss of cognitive enhancement when using large amounts, large doses of methylphenidate can induce side effects that impair athletic performance, such as rhabdomyolysis and hyperthermia.[medical citation needed]


Animal studies using rats with ADHD-like behaviours were used to assess the safety of methylphenidate on the developing brain and found that psychomotor impairments, structural and functional parameters of the dopaminergic system were improved with treatment. This animal data suggests that methylphenidate supports brain development and hyperactivity in children diagnosed with ADHD. However, in normal control animals methylphenidate caused long lasting changes to the dopaminergic system suggesting that if a child is misdiagnosed with ADHD they may be at risk of long lasting adverse effects to brain development.[examples needed] Animal tests found that rats given methylphenidate grew up to be more stressed and emotional.[clarification needed] It is unclear due to lack of follow-up study whether this occurs in ADHD like animals[clarification needed] and whether it occurs in humans.[51] However, long lasting benefits of stimulant drugs have not been found in humans.[52]

Side effects

Some adverse effects may emerge during chronic use of methylphenidate so a constant watch for adverse effects is recommended.[53] The adverse effects of methylphenidate include:[54]

Recent large-scale studies by the US FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the medical use of amphetamine, methylphenidate, or other commonly prescribed ADHD stimulants.[58][59][60][61]

On occasion, stimulant psychosis can occur during long-term therapy with methylphenidate. Regular psychiatric monitoring of people who are taking methylphenidate for adverse effects such as psychotic symptomatology has been recommended.[62]

Addiction and dependence

Addiction and psychological dependence are possible with methylphenidate. Pharmacological texts describe methylphenidate as a stimulant with effects and abuse potential similar to the amphetamines.[63]

As with many drugs, ΔFosB may be implicated in methylphenidate addiction.

Methylphenidate has shown some benefits as a replacement therapy for individuals who are addicted to and dependent upon methamphetamine.[64] Methylphenidate and amphetamine have been investigated as a chemical replacement for the treatment of cocaine addiction[65][66][67][68] in the same way that methadone is used as a replacement drug for physical dependence upon heroin. Its effectiveness in treatment of cocaine or psychostimulant addiction or psychological dependence has not been proven and further research is needed.[69]



Intake of adrenergic agonist drugs or pemoline with methylphenidate increases the risk of liver toxicity.[70][71]

When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification,[72][73] not unlike the hepatic formation of cocaethylene from cocaine and alcohol. The reduced potency of ethylyphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses and even in overdose cases ethylphenidate concentrations remain negligible.[12][74]

Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%.[75]


Methylphenidate is contraindicated by the United States Food and Drug Administration for individuals using monoamine oxidase inhibitors (e.g., phenelzine and tranylcypromine), or individuals suffering from agitation, tics, or glaucoma, or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals.[76]


The U.S. FDA gives methylphenidate a pregnancy category of C, and women are advised to only use the drug if the benefits outweigh the potential risks.[77] Not enough animal and human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development. In 2007, empirical literature included 63 cases of prenatal exposure to methylphenidate across three empirical studies.[78] One of these studies (N = 11) demonstrated no significant increases in malformations.[79] A second (N = 13) demonstrated one major malformation in newborns with early exposure to methylphenidate, which was in the expected range of malformations. However, this was a cardiac malformation, which was not within the statistically expected range.[80] Finally, in a retrospective analysis of patients' medical charts (N = 38), researchers examined the relationship between abuse of intravenous methylphenidate and pentazocine in pregnant women. Twenty-one percent of these children were born prematurely, and several had stunted growth and withdrawal symptoms (31% and 28%, respectively). Intravenous methylphenidate abuse was confounded with the concurrent use of other substances (e.g., cigarettes, alcohol) during pregnancy.

Overdose and toxicology

In the majority of unremarkable isolated cases MPH overdose is asymptomatic (symptomless) or only incurs minor symptoms even in children under age 6.[81][82][83] In cases that manifest symptoms, these can typically include agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia.[84] LD50 in mice is 190 mg/kg.[85]

Studies of reported incidents tend to show that most overdoses are unintentional and generally conclude that severe or major toxicity are comparatively rare events (none in the Michigan study of 289 incidents,[81] 0.9% in the 2004 US national analysis with n=8336,[86] and 0.2% in the same analysis for 2010 with n=6503[82]).

Death rates are also comparatively low (none in the Michigan study, 0.36 per 1000 with n=3 for the 2004 US national analysis, 0.15 per 1000 with n=1 for the 2010 analysis; the US national guideline approved 2007 also notes only 2 deaths reported as primarily to MPH overdose from 2000–2005[83]).

A 2011 Swiss study also agreed with the general findings, adding a cautionary note that serious or severe outcomes such as necrosis, abscess and amputation had occurred as a result of severe toxicity at the injection site in 3 cases of abuse via arterial injection.[87]

Medical and emergency handling

Key recommendations in US guidelines for overdose handling include:[83]

  • Well evidenced findings (evidence standard "A"): 0–6 years: <2 mg/kg rarely causes serious toxicity, 0–5 years: up to 40 mg well tolerated, 6–12 years: up to 80 mg well tolerated;
  • Evidence grade "B" and "C": If <6 years and >2 mg/kg, or <60 kg and >1 mg/kg, or ≥60 kg and >60 mg: refer to emergency help;
  • Tentative only (D): 4 mg/kg or 120 mg of intact modified (slow) release version: refer to emergency help.
  • Symptoms (D): "Patients experiencing any changes in behavior other than mild stimulation or agitation should be referred to an emergency department. Examples of moderate to severe symptoms that warrant referral include moderate-to-severe agitation, hallucinations, abnormal muscle movements, headache, chest pain, loss of consciousness, or convulsions".
  • Other factors: Cases of intent, malicious administration (by another), as well as monoamine oxidase inhibitor (MAOI) users should always be referred to emergency help;
  • Passage of time/delay: Patients where more than 3 hours have passed without symptoms do not usually need referral to emergency help.
  • Benzodiazepines may be used as treatment if agitation, dystonia, or convulsions are present.

Poison control center analyses and study findings

A study in 2000 looked in detail at all 289 overdoses of MPH reported to the Children's Hospital of Michigan regional poison control center during 1993 and 1994 (excluded: 105 extended-release formulations or co-ingestants, to ensure MPH overdose effects were not confounded by other effects).[81] The case histories were: Age: 251 aged under 18, 38 adult; Reason: 68 (23%) intentional/unknown/error. In 163 cases (56%) the dose was known and in 41% the patient's own MPH was involved. Variation in overdose ranged from <1 mg/kg (30%) to >3 mg/kg (7.5%) mean 1.7 mg/kg. Findings:

  • No patient developed "severe" symptoms, but "less favourable" symptoms were seen with intentional overdoses. In overdoses below 2 mg/kg the majority (63–75%) suffered no effect and a minority (9–16%) suffered a moderate effect. Above 3 mg/kg around 27% suffered a moderate effect. Overall symptoms occurred in 31% of all overdoses. In paediatric exposures 29% developed symptoms but 66% suffered no clinical effects (mild/moderate effects: 34%). Symptomatic findings were:[81]
  • "Intentional ingestion of MPH was most commonly associated with isolated symptoms of tachycardia, agitation, lethargy, vomiting, dizziness, mydriasis, and tremor. Of the 8 patients in this group who manifested multiple symptoms, erythema, diaphoresis, hypertension, emesis, chest pain, tremor, fever, and insomnia"
  • Symptoms were common (33%) in the 0–5 age group: "Isolated lethargy, agitation, headache, and vomiting were most commonly seen. One patient in this group developed dystonia, and two developed agitation in combination with hypertension or tachycardia."

In 2004, the American Association of Poison Control Centers Toxic Exposure Surveillance System annual report showed about 8300 methylphenidate ingestions reported in US poison center data,[83][86] of which 72% were accidental or unintended, and 19% involved children age 0–6. The most common reasons for intentional exposure were drug abuse and suicide attempts.[88] The 2010 report[82] showed 6500 single reported exposures in the US for the year. 2010 incidents:

  • By age: 0–5: 24%, 6–12: 38%, 13–19:21%, 20+: 16%, other adult: 1%.
  • By cause: accident/error: 79%, intended: 18%, other: 3%.
  • By outcome: moderate: 624, major:13, death:1, others were no outcome, minor, or unknown. (2004 outcomes: moderate: 940, major: 73, death: 3)[86]

A Swiss study in 2011 also concurred, noting similar findings in several studies and national analyses in that country, but noted that these findings were potentially inapplicable to the few cases of abuse via crushed MPH injection, which was the sole situation where "serious" or "severe" local toxicity was observed, leading in their study to pain, necrosis and partial limb or digit amputation in two of 14 adult cases over 8 years (14%) who mistakenly injected arterially, and inguinal abscess and fever in one who injected intravenously.[87]

Abuse potential

Legal warning printed on Ritalin packaging

Methylphenidate was classified as a Schedule II drug in the United States in 1971 after reports of intravenous abuse beginning in 1963 and oral abuse in 1971. The first death by IV abuse was noted by 1986, abuse by family members of prescription recipients by 1988, intranasal abuse by 1991, and deaths from intranasal abuse as well as intranasal abuse by health professionals were seen by 1995.[63] A 1998 longitudinal study noted that 16% of schoolchildren prescribed methylphenidate were either abusing the drug or had been asked to divert it, while none of the children involved recognized that it had any potential for abuse.[63] A 2008 review noted recreation or study use was "fairly common" in US university studies and that the risk could only be said to be low "in the short term" since there was little certainty about long-term effects of overdose and abuse.[89]

Methylphenidate has potential for abuse due to its action on dopamine transporters. Methylphenidate, like other stimulants, increases dopamine levels in the brain. According to one study, at therapeutic doses this increase is slow, and thus euphoria only rarely occurs even when it is administered intravenously.[90] A review of other studies indicates that the abuse potential of methylphenidate is comparable to that of amphetamines and that intravenous use resulted in a "high" subjectively similar to cocaine. The DSM-IV "does not differentiate between amphetamines and methylphenidate in regard to the signs and symptoms of toxicity."[63]

At therapeutic doses, the abuse and addiction potential of methylphenidate may be lower than that of other dopaminergic stimulants.[90][91] The abuse potential is increased when methylphenidate is crushed and insufflated (snorted), or injected.[92] However, the dose that produces euphoric effects varies among individuals. The primary source of methylphenidate for abuse is diversion from legitimate prescriptions, rather than illicit synthesis. Those who use methylphenidate medicinally generally take it orally, while intranasal and intravenous are the preferred means for recreational use.[84] IV users tend to be adults whose use may cause panlobular pulmonary emphysema.[88]

Abuse of prescription stimulants is higher amongst college students than non-college attending young adults. College students use methylphenidate either as a study aid or to stay awake longer. Increased alcohol consumption due to stimulant misuse has additional negative effects on health.[93]

Recreational users may crush the tablets and insufflate the powder[medical citation needed] This method will increase bioavailability and produce a much more rapid onset of effects than when taken orally; however the overall duration of action tends to be decreased by any non-oral use of drug preparations made for oral use.[medical citation needed]

Ethics of use for performance enhancement

Methylphenidate is sometimes used by students to enhance their mental abilities, improving their concentration and helping them to study.

John Harris, an expert in bioethics, has said that it would be unethical to stop healthy people taking the drug. He also argues that it would be "not rational" and against human enhancement to not use the drug to improve people's cognitive abilities.[94] Anjan Chatterjee however has warned that there is a high potential for abuse and may cause serious adverse effects on the heart, meaning that only people with an illness should take the drug. In the British Medical Journal he wrote that it was premature to endorse the use of Ritalin in this way as the effects of the drug on healthy people have not been studied.[95][96]

Barbara Sahakian has argued that the use of Ritalin in this way may give students an unfair advantage in examinations and that as a result universities may want to discuss making students give urine samples to be tested for the drug.[97]



Methylphenidate primarily acts as a dopamine-norepinephrine reuptake inhibitor (NDRI). It is a benzylpiperidine and phenethylamine derivative which also shares part of its basic structure with catecholamines.

Methylphenidate is most active at modulating levels of dopamine and to a lesser extent norepinephrine.[98] Methylphenidate binds to and blocks dopamine transporters and norepinephrine transporters.[99]

While both amphetamine and methylphenidate are dopaminergic, it should be noted that their methods of action are distinct. Specifically, methylphenidate is a dopamine reuptake inhibitor while amphetamine is both a releasing agent and reuptake inhibitor of dopamine and norepinephrine. Each of these drugs has a corresponding effect on norepinephrine which is weaker than its effect on dopamine. Methylphenidate's mechanism of action at dopamine-norepinephrine release is still debated, but is fundamentally different from most other phenethylamine derivatives, as methylphenidate is thought to increase general firing rate, whereas amphetamine reduces firing rate and reverses the flow of the monoamines via TAAR1 activation.[100][101][102][103][104]

Methylphenidate has both dopamine transporter and norepinephrine transporter binding affinity, with the dextromethylphenidate enantiomers displaying a prominent affinity for the norepinephrine transporter. Both the dextrorotary and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT1A and 5HT2B subtypes, though direct binding to the serotonin transporter was not observed.[105] A later study confirmed the d-threo- enantiomer binding to the 5HT1A receptor, but no significant activity on the 5HT2B receptor was found.[106]

Methylphenidate may protect neurons from the neurotoxic effects of Parkinson's disease and methamphetamine abuse.[107]

The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate.[98]

Methylphenidate has been identified as a sigma-1 receptor agonist.[108]

Binding profile of methylphenidate[109]

Transporter Ki (nM)
SERT >10000
NET 345.1
DAT 41

(For more tables of binding profiles for methylphenidate derivatives see: List of methylphenidate analogues)


Methylphenidate taken orally has a bioavailability of 11–52% with a duration of peak action around 2–4 hours for instant release (i.e. Ritalin), 3–8 hours for sustained release (i.e. Ritalin SR), and 8–12 hours for extended release (i.e. Concerta). The half-life of methylphenidate is 2–3 hours, depending on the individual. The peak plasma time is achieved at about 2 hours.[110]

d-Methylphenidate is much more bioavailable than l-methylphenidate when administered orally, and is primarily responsible for the psychoactivity of racemic methylphenidate.[111]

Contrary to the expectation, taking methylphenidate with a meal speeds absorption.[112]

Detection in biological fluids

The concentration of methylphenidate or ritalinic acid, its major metabolite, may be quantified in plasma, serum or whole blood in order to monitor compliance in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.[113]


Four isomers of methylphenidate are known to exist. One pair of threo isomers and one pair of erythro are distinguished, from which only d-threo-methylphenidate exhibits the pharmacologically usually desired effects.[98][114] When the drug was first introduced it was sold as a 3:1 mixture of erythro:threo diastereomers. The erythro diastereomers are also pressor amines. "TMP" is referring only to the threo product that does not contain any erythro diastereomers. Since the threo isomers are energetically favored, it is easy to epimerize out any of the undesired erythro isomers. The drug that contains only dextrorotary methylphenidate is called d-TMP. A review on the synthesis of enantiomerically pure (2R,2'R)-(+)-threo-methylphenidate hydrochloride has been published.[115]

Methylphenidate synthesis
Method 1: Methylphenidate preparation according to Jeffrey M. Axten et al. (1998)[116]
Method 2: Alternate methylphenidate synthesis[117]

Production and brand-names

File:Ritalin Methylphenidat.jpg
German "Ritalin" brand methylphenidate

Methylphenidate is produced in the United States, Mexico, Spain, Sweden, Pakistan, and India. Ritalin is also sold in Canada, Australia, the United Kingdom, Spain, Germany and other European countries (although in much lower volumes than in the United States). Other brands include Concerta, Methylin, and Daytrana, and generic forms, including Methylin, Metadate, Phenida and Attenta are produced by numerous pharmaceutical companies throughout the world. In Belgium the product is sold under the name Rilatine and in Brazil, Portugal and Argentina as Ritalina. In Thailand, it is found under the name Hynidate. In India, it is found under the names Addwize and Inspiral SR.

The dextrorotary enantiomer of methylphenidate, known as dexmethylphenidate, is sold as a generic and under the brand names Focalin and Attenade.

Available forms

File:Methylphenidate Formulations.jpg
Clockwise from top: Concerta 18 mg (OROS), Medikinet 5 mg, Methylphenidat TAD 10 mg, Ritalin 10 mg (immediate release tablets), Medikinet XL 30 mg (CR capsule).

Methylphenidate is available in numerous forms, a doctor will prescribe the appropriate method based on patient feedback and product availability. Current available forms are tablet, capsule, adhesive-based matrix transdermal system (patch), and oral suspension (liquid syrup).


File:Ritalin Pill.jpg
Ritalin 10 mg tablet

A formulation by the Novartis trademark name Ritalin, is an immediate-release racemic mixture, although a variety of formulations and generic brand names exist. Generic brand names include Ritalina, Rilatine, Attenta, Medikinet, Metadate, Methylin, Penid, Tranquilyn and Rubifen. Focalin is a preparation containing only dextro-methylphenidate, rather than the usual racemic dextro- and levo-methylphenidate mixture of other formulations.


Extended-release tablets, capsules and liquid suspension include:

  • Concerta (brand-name); Watson methylphenidate ER (US generic); Teva-Methylphenidate ER‑C (Canadian generic). Each pill is effective for 12 hours.[118]
  • Equasym XL; Medikinet XL; Metadate CD; Ritalin LA; Rubifen SR. Some of these work identically to each other; some do not.
  • Ritalin‑SR (brand-name); Methylin ER (US generic); Metadate ER (US generic); methylphenidate SR (Canadian generic).[119][120][121] Each pill is effective for 5–8 hours.[118]

A newer way of taking methylphenidate is by using a transdermal patch (under the brand name Daytrana), similar to those used for nicotine replacement therapy.

Concerta tablets are marked with the letters "ALZA" and followed by: "18", "27", "36", or "54", relating to the mg dosage strength. Approximately 22% of the dose is immediate release,[122] and the remaining 78% of the dose is released over 10–12 hours post ingestion, with an initial increase over the first 6 to 7 hours, and subsequent decline in released drug.[123]

Ritalin LA capsules are marked with the letters "NVR" (abbrev.: Novartis) and followed by: "R20", "R30", or "R40", depending on the (mg) dosage strength. Both Ritalin LA[124] and Equasym XL provide two standard doses – half the total dose being released immediately and the other half released four hours later. In total, each capsule is effective for about eight hours.

Metadate CD capsules contain two types of beads; 30% of the beads are immediate release, and the other 70% of the beads are evenly sustained release.[125]

Quillivant XR (brand name) is an extended-release oral suspension (after reconstitution with water): 25 mg per 5 mL (5 mg per mL). It was designed and is patented and made by Pfizer. The medication comes in various sizes from 60ml to 180ml (after reconstitution). Each bottle is shipped with the medication in powder form containing roughly 20% instant-release and 80% extended-release methylphenidate, to which water must be added by the pharmacist in an amount corresponding with the total intended volume of the bottle. The bottle must be shaken vigorously for ten seconds prior to administration via included oral syringe to ensure proper ratio.[126]

History, society, and culture

Methylphenidate was first synthesized in 1944,[127] and was identified as a stimulant in 1954.[128]

Methylphenidate was synthesized by Ciba (now Novartis) chemist Leandro Panizzon. His wife, Marguerite, had low blood pressure and would take the drug as a stimulant before playing tennis. He named the substance Ritaline, after his wife's nickname, Rita.[129]

Originally it was marketed as a mixture of two racemates, 80% (±)-erythro and 20% (±)-threo. Subsequent studies of the racemates showed that the central stimulant activity is associated with the threo racemate and were focused on the separation and interconversion of the erythro isomer into the more active threo isomer.[130][131][132]

Methylphenidate was first used to allay barbiturate-induced coma, narcolepsy and depression.[129] It was later used to treat memory deficits in the elderly.[133] Beginning in the 1960s, it was used to treat children with ADHD or ADD, known at the time as hyperactivity or minimal brain dysfunction (MBD) based on earlier work starting with the studies by American psychiatrist Charles Bradley[134] on the use of psychostimulant drugs, such as benzedrine, with then called "maladjusted children".[135] Production and prescription of methylphenidate rose significantly in the 1990s, especially in the United States, as the ADHD diagnosis came to be better understood and more generally accepted within the medical and mental health communities.[136]

In 2000 Janssen received U.S. Food and Drug Administration (FDA) approval to market "Concerta", an extended-release form of Ritalin.[137] See the "Extended-release" section of this article, above, for more information about Concerta.

Legal status

  • Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.[138]
  • In the United States, methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high potential for abuse.
  • In the United Kingdom, methylphenidate is a controlled 'Class B' substance. Possession without prescription carries with a sentence up to 5 years and/or an unlimited fine, and supplying it is 14 years and/or an unlimited fine.[139]
  • In Canada, methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline, among others), and is illegal to possess without a prescription, pursuant to Part G (section G.01.002) of the Food and Drug Regulations under the Food and Drugs Act.
  • In New Zealand, methylphenidate is a 'class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and distribution of it is punishable by a 14-year sentence.
  • In Australia, methylphenidate is a 'Schedule 8' controlled substance. Such drugs must be kept in a lockable safe before being handed out and possession without prescription carries hefty fines and even imprisonment.
  • In Sweden, methylphenidate is a List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison.[140]
  • In France, methylphenidate is covered by the "narcotics" schedule, prescription and distribution conditions are restricted with hospital-only prescription for the initial treatment and yearly consultations.[141]


Methylphenidate has been the subject of controversy in relation to its use in the treatment of ADHD. One such criticism is prescribing psychostimulants medication to children to reduce ADHD symptoms.[142] The contention that methylphenidate acts as a gateway drug has been discredited by multiple sources,[143] according to which abuse is statistically very low and "stimulant therapy in childhood does not increase the risk for subsequent drug and alcohol abuse disorders later in life".[144]

Another controversy concerns the narrow definition of ADHD as the clinical criterion for prescribing Methylphenidate. It has shown for instance that the effect of methylphenidate on adults with no ADHD approaches its effect in adults with ADHD.[145] Hence, it may be effective for individuals with acute problems leading to difficulty to concentrate irrespectively of ADHD diagnosis. In Israel, for example, since 2011 general MDs can prescribe methylphenidate with no ADHD diagnosis, for a constrained time period.

Treatment of ADHD by way of Methylphenidate has led to legal actions including malpractice suits regarding informed consent, inadequate information on side effects, misdiagnosis, and coercive use of medications by school systems.[146] In the U.S. and the United Kingdom, it is approved for use in children and adolescents. In the U.S., the Food and Drug Administration approved the use of methylphenidate in 2008 for use in treating adult ADHD.[147] In the United Kingdom, while not licensed for use in Adult ADHD, NICE guidelines suggest it be prescribed off-license for the condition.[148] Methylphenidate has been approved for adult use in the treatment of narcolepsy.[149]

The pharmacological effects of methylphenidate resemble those of the class of DNRIs,[150] which is useful in the treatment of ADHD.[151] Shortages of Ritalin in 2011 have been blamed on overmedication.[152]

A study found that ADHD medication was not associated with increased risk of cigarette use, and in fact stimulant treatments such as Ritalin seemed to lower this risk.[153]


  1. ^ This involves impaired dopamine neurotransmission in the mesocortical and mesolimbic pathways and norepinephrine neurotransmission in the prefrontal cortex and locus coeruleus.[32]

See also


  1. ^
  2. ^ a b "Chemical and Physical Properties". Methylphenidate. Pubchem Compound. National Center for Biotechnology Information. Retrieved 24 June 2014. 
  3. ^ Markowitz JS, Straughn AB, Patrick KS (2003). "Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder: focus on methylphenidate formulations". Pharmacotherapy 23 (10): 1281–99. PMID 14594346. doi:10.1592/phco.23.12.1281.32697. 
  4. ^
  5. ^ Diller, Lawrence (1999). Running on Ritalin. ISBN 978-0553379068. 
  6. ^ Lange KW, Reichl S, Lange KM, Tucha L, Tucha O (2010). "The history of attention deficit hyperactivity disorder". ADHD Attention Deficit and Hyperactivity Disorders 2 (4): 241–55. PMC 3000907. PMID 21258430. doi:10.1007/s12402-010-0045-8. 
  7. ^
  8. ^
  9. ^ "Functional Roles of Norepinephrine and Dopamine in ADHD: Dopamine in ADHD". Medscape. 2006. Retrieved 8 October 2013. Catecholamines not only facilitate attention, they are essential to executive function. The prefrontal cortex directs behaviors, thoughts, and feelings represented in working memory. This representational knowledge is essential to fundamental cognitive abilities that compromise executive functions. These encompass the ability to (1) inhibit inappropriate behaviors and thoughts, (2) regulate our attention, (3) monitor our actions, and (4) plan and organize for the future. Difficulties with these prefrontal cortex functions are evident in neuropsychological and imaging studies of ADHD patients and account for many of the common behavioral symptoms. Measures of prefrontal cortical functioning in animals indicate that these functions are sensitive to small changes in catecholamine modulation of prefrontal cortex cells that can produce profound effects on the ability of the prefrontal cortex to guide behavior. Optimal levels of NE acting at postsynaptic alpha2A-adrenoceptors and dopamine acting at D1 receptors are essential to prefrontal cortex function. Blockade of norepinephrine alpha2-adrenoceptors in prefrontal cortex markedly impairs prefrontal cortex function and mimics most of the symptoms of ADHD, including impulsivity and locomotor hyperactivity. Conversely, stimulation of prefrontal cortical alpha2-adrenoceptors strengthens prefrontal cortex regulation of behavior and reduces distractibility. Thus, effective treatments for ADHD facilitate catecholamine transmission and apparently have their therapeutic actions by optimizing catecholamine actions in the prefrontal cortex 
  10. ^ Arnsten AF, Li BM (2005). "Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions". Biological Psychiatry 57 (11): 1377–84. PMID 15950011. doi:10.1016/j.biopsych.2004.08.019. 
  11. ^
  12. ^ a b Markowitz JS, Logan BK, Diamond F, Patrick KS (1999). "Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion". Journal of Clinical Psychopharmacology 19 (4): 362–6. PMID 10440465. doi:10.1097/00004714-199908000-00013. 
  13. ^ Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE (2006). "A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder" (PDF). Can J Clin Pharmacol 13 (1): e50–62. PMID 16456216. 
  14. ^ Gilmore A, Milne R (2001). "Methylphenidate in children with hyperactivity: review and cost-utility analysis". Pharmacoepidemiol Drug Saf 10 (2): 85–94. PMID 11499858. doi:10.1002/pds.564. 
  15. ^ Mott TF, Leach L, Johnson L (2004). "Clinical inquiries. Is methylphenidate useful for treating adolescents with ADHD?". The Journal of Family Practice 53 (8): 659–61. PMID 15298843. 
  16. ^ Vitiello B (2001). "Psychopharmacology for young children: clinical needs and research opportunities". Pediatrics 108 (4): 983–9. PMID 11581454. doi:10.1542/peds.108.4.983. 
  17. ^ Hermens DF, Rowe DL, Gordon E, Williams LM (2006). "Integrative neuroscience approach to predict ADHD stimulant response". Expert Review of Neurotherapeutics 6 (5): 753–63. PMID 16734523. doi:10.1586/14737175.6.5.753. 
  18. ^ Bernardo Dell’Osso, Cristina Dobrea, Laura Cremaschi, Chiara Arici, A. Carlo Altamura (2014). "Wake-Promoting Pharmacotherapy for Psychiatric Disorders". Current Psychiatry Reports 16 (12): 524. PMID 25312027. doi:10.1007/s11920-014-0524-2. 
  19. ^ Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. PMID 23247506. doi:10.1001/jamapsychiatry.2013.277. 
  20. ^ Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. PMC 3801446. PMID 24107764. doi:10.4088/JCP.12r08287. 
  21. ^ Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. PMID 22118249. doi:10.1111/j.1600-0447.2011.01786.x. Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. 
  22. ^ a b c Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 9781441913968. 
  23. ^ a b Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. PMID 21699268. doi:10.2165/11589380-000000000-00000. 
  24. ^ Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123. ISBN 9781441913968. 
  25. ^ Fone KC, Nutt DJ (2005). "Stimulants: use and abuse in the treatment of ADD". Current Opinion in Pharmacology 5 (1): 87–93. PMID 15661631. doi:10.1016/j.coph.2004.10.001. 
  26. ^ Capp PK, Pearl PL, Conlon C (2005). "Methylphenidate HCl: therapy for attention deficit hyperactivity disorder". Expert Rev Neurother 5 (3): 325–31. PMID 15938665. doi:10.1586/14737175.5.3.325. 
  27. ^ Greenfield B, Hechman L (2005). "Treatment of attention deficit hyperactivity disorder in adults". Expert Rev Neurother 5 (1): 107–21. PMID 15853481. doi:10.1586/14737175.5.1.107. 
  28. ^ Faraone SV, Wilens TE (2007). "Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion". J Clin Psychiatry. 68 Suppl 11: 15–22. PMID 18307377. doi:10.4088/jcp.1107e28. 
  29. ^ Wilens TE, Faraone SV, Biederman J, Gunawardene S (2003). "Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature". Pediatrics 111 (1): 179–85. PMID 12509574. doi:10.1542/peds.111.1.179. 
  30. ^ Advokat C (2010). "What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD)". Neurosci Biobehav Rev 34 (8): 1256–66. PMID 20381522. doi:10.1016/j.neubiorev.2010.03.006. 
  31. ^ Stevenson RD, Wolraich ML (1989). "Stimulant medication therapy in the treatment of children with attention deficit hyperactivity disorder". Pediatr. Clin. North Am. 36 (5): 1183–97. PMID 2677938. 
  32. ^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 154–157. ISBN 9780071481274. 
  33. ^ a b c "Stimulants for Attention Deficit Hyperactivity Disorder". WebMD. Healthwise. 12 April 2010. Retrieved 12 November 2013. 
  34. ^ Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S (February 2002). "Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults". J. Am. Acad. Child Adolesc. Psychiatry 41 (2 Suppl): 26S–49S. PMID 11833633. doi:10.1097/00004583-200202001-00003. 
  35. ^ Rosack Jim (2 January 2004). "Brain Scans Reveal Physiology of ADHD". Psychiatric News 39 (1): 26. [dead link]
  36. ^ Liddle EB, Hollis C, Batty MJ, Groom MJ, Totman JJ, Liotti M, Scerif G, Liddle PF (2011). "Task-related default mode network modulation and inhibitory control in ADHD: Effects of motivation and methylphenidate". Journal of Child Psychology and Psychiatry 52 (7): 761–71. PMID 21073458. doi:10.1111/j.1469-7610.2010.02333.x. 
  37. ^ Lichtenstein P, Halldner L, Zetterqvist J, Sjölander A, Serlachius E, Fazel S, Långström N, Larsson H (2012). "Medication for Attention Deficit–Hyperactivity Disorder and Criminality". New England Journal of Medicine 367 (21): 2006–14. PMC 3664186. PMID 23171097. doi:10.1056/NEJMoa1203241. 
  38. ^ Pappadopulos E, Woolston S, Chait A, Perkins M, Connor DF, Jensen PS (2006). "Pharmacotherapy of aggression in children and adolescents: Efficacy and effect size". Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 15 (1): 27–39. PMC 2277275. PMID 18392193. 
  39. ^ Fry JM (1998). "Treatment modalities for narcolepsy". Neurology 50 (2 Suppl 1): S43–8. PMID 9484423. doi:10.1212/WNL.50.2_Suppl_1.S43. 
  40. ^ Mitler MM (1994). "Evaluation of treatment with stimulants in narcolepsy". Sleep 17 (8 Suppl): S103–6. PMID 7701190. 
  41. ^ Kraus MF, Burch EA (1992). "Methylphenidate hydrochloride as an antidepressant: controversy, case studies, and review". South. Med. J. 85 (10): 985–91. PMID 1411740. doi:10.1097/00007611-199210000-00012. 
  42. ^ Rozans M, Dreisbach A, Lertora JJ, Kahn MJ (2002). "Palliative uses of methylphenidate in patients with cancer: a review". J. Clin. Oncol. 20 (1): 335–9. PMID 11773187. doi:10.1200/JCO.20.1.335. 
  43. ^ Leonard BE, McCartan D, White J, King DJ (2004). "Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects". Hum Psychopharmacol 19 (3): 151–80. PMID 15079851. doi:10.1002/hup.579. 
  44. ^ Satel SL, Nelson JC (1989). "Stimulants in the treatment of depression: a critical overview". J Clin Psychiatry 50 (7): 241–9. PMID 2567730. 
  45. ^ Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.: 1–21. PMID 25591060. doi:10.1162/jocn_a_00776. The present meta-analysis was conducted to estimate the magnitude of the effects of methylphenidate and amphetamine on cognitive functions central to academic and occupational functioning, including inhibitory control, working memory, short-term episodic memory, and delayed episodic memory. In addition, we examined the evidence for publication bias. Forty-eight studies (total of 1,409 participants) were included in the analyses. We found evidence for small but significant stimulant enhancement effects on inhibitory control and short-term episodic memory. Small effects on working memory reached significance, based on one of our two analytical approaches. Effects on delayed episodic memory were medium in size. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets of healthy cognition is probably modest overall. In some situations, a small advantage may be valuable, although it is also possible that healthy users resort to stimulants to enhance their energy and motivation more than their cognition. ... Earlier research has failed to distinguish whether stimulants’ effects are small or whether they are nonexistent (Ilieva et al., 2013; Smith & Farah, 2011). The present findings supported generally small effects of amphetamine and methylphenidate on executive function and memory. Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ...

    The results of this meta-analysis cannot address the important issues of individual differences in stimulant effects or the role of motivational enhancement in helping perform academic or occupational tasks. However, they do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.
  46. ^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 318. ISBN 9780071481274. Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors. 
  47. ^ a b c Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacol. Rev. 66 (1): 193–221. PMID 24344115. doi:10.1124/pr.112.007054. 
  48. ^ Twohey M (26 March 2006). "Pills become an addictive study aid". JS Online. Archived from the original on 15 August 2007. Retrieved 2 December 2007. 
  49. ^ Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ (October 2006). "Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration". Pharmacotherapy 26 (10): 1501–1510. PMC 1794223. PMID 16999660. doi:10.1592/phco.26.10.1501. 
  50. ^ Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med. 43 (5): 301–311. PMID 23456493. doi:10.1007/s40279-013-0030-4. 
  51. ^ Grund T, Lehmann K, Bock N, Rothenberger A, Teuchert-Noodt G (2006). "Influence of methylphenidate on brain development—an update of recent animal experiments". Behav Brain Funct 2: 2. PMC 1363724. PMID 16403217. doi:10.1186/1744-9081-2-2. 
  52. ^ Sagvolden T, Sergeant JA (1998). "Attention deficit/hyperactivity disorder—from brain dysfunctions to behaviour". Behav. Brain Res. 94 (1): 1–10. PMID 9708834. doi:10.1016/S0166-4328(97)00164-2. 
  53. ^ Gordon N (1999). "Attention deficit hyperactivity disorder: possible causes and treatment". Int. J. Clin. Pract. 53 (7): 524–8. PMID 10692738. 
  54. ^ – Ritalin Side Effects. Retrieved on 16 October 2011.
  55. ^ "Methylphenidate ADHD Medications: Drug Safety Communication – Risk of Long-lasting Erections". U.S. Food and Drug Administration. 17 December 2013. Retrieved 17 December 2013. 
  56. ^ Jaanus SD (1992). "Ocular side-effects of selected systemic drugs". Optom Clin 2 (4): 73–96. PMID 1363080. 
  57. ^ Auger RR, Goodman SH, Silber MH, Krahn LE, Pankratz VS, Slocumb NL (2005). "Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study". Sleep 28 (6): 667–72. PMID 16477952. 
  58. ^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults". United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013. 
  59. ^ Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med. 365 (20): 1896–1904. PMID 22043968. doi:10.1056/NEJMoa1110212. 
  60. ^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults". United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013. 
  61. ^ Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA 306 (24): 2673–2683. PMC 3350308. PMID 22161946. doi:10.1001/jama.2011.1830. 
  62. ^ Kraemer M, Uekermann J, Wiltfang J, Kis B (July 2010). "Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature". Clin Neuropharmacol 33 (4): 204–6. PMID 20571380. doi:10.1097/WNF.0b013e3181e29174. 
  63. ^ a b c d Morton WA, Stockton GG (2000). "Methylphenidate Abuse and Psychiatric Side Effects". Prim Care Companion J Clin Psychiatry 2 (5): 159–164. PMC 181133. PMID 15014637. doi:10.4088/PCC.v02n0502. 
  64. ^ Elkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J (2008). "Pharmacotherapy of methamphetamine addiction: an update". Substance Abuse 29 (3): 31–49. PMC 2597382. PMID 19042205. doi:10.1080/08897070802218554. 
  65. ^ Grabowski J, Roache JD, Schmitz JM, Rhoades H, Creson D, Korszun A (1997). "Replacement medication for cocaine dependence: methylphenidate". J Clin Psychopharmacol 17 (6): 485–8. PMID 9408812. doi:10.1097/00004714-199712000-00008. 
  66. ^ Gorelick DA, Gardner EL, Xi ZX (2004). "Agents in development for the management of cocaine abuse". Drugs 64 (14): 1547–73. PMID 15233592. doi:10.2165/00003495-200464140-00004. 
  67. ^ Karila L, Gorelick D, Weinstein A, Noble F, Benyamina A, Coscas S, Blecha L, Lowenstein W, Martinot JL, Reynaud M, Lépine JP (2008). "New treatments for cocaine dependence: a focused review". Int. J. Neuropsychopharmacol. 11 (3): 425–38. PMID 17927843. doi:10.1017/S1461145707008097. 
  68. ^ "NIDA InfoFacts: Understanding Drug Abuse and Addiction" (PDF). 2008. 
  69. ^ Shearer J (2008). "The principles of agonist pharmacotherapy for psychostimulant dependence". Drug Alcohol Rev 27 (3): 301–8. PMID 18368612. doi:10.1080/09595230801927372. 
  70. ^ Roberts SM, DeMott RP, James RC (1997). "Adrenergic modulation of hepatotoxicity". Drug Metab. Rev. 29 (1–2): 329–53. PMID 9187524. doi:10.3109/03602539709037587. 
  71. ^ Marotta PJ, Roberts EA (1998). "Pemoline hepatotoxicity in children". The Journal of Pediatrics 132 (5): 894–7. PMID 9602211. doi:10.1016/S0022-3476(98)70329-4. 
  72. ^ Patrick KS, González MA, Straughn AB, Markowitz JS (2005). "New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder". Expert Opinion on Drug Delivery 2 (1): 121–43. PMID 16296740. doi:10.1517/17425247.2.1.121. 
  73. ^ Markowitz JS, DeVane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, Patrick KS (2000). "Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol". Drug Metabolism and Disposition 28 (6): 620–4. PMID 10820132. 
  74. ^ Markowitz JS, DeVane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, Patrick KS (2000). "Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol". Drug metabolism and disposition: the biological fate of chemicals 28 (6): 620–4. PMID 10820132. 
  75. ^ Patrick KS, Straughn AB, Perkins JS, González MA (2009). "Evolution of stimulants to treat ADHD: transdermal methylphenidate". Human Psychopharmacology 24 (1): 1–17. PMC 2629554. PMID 19051222. doi:10.1002/hup.992. 
  76. ^ "DAYTRANA" (PDF). United Stated Food and Drug Administration. Noven Pharmaceuticals, Inc. October 2013. Retrieved 13 June 2014. 
  77. ^ Methylphenidate Use During Pregnancy and Breastfeeding. Retrieved on 30 April 2011.
  78. ^ Humphreys C, Garcia-Bournissen F, Ito S, Koren G (2007). "Exposure to attention deficit hyperactivity disorder medications during pregnancy". Canadian Family Physician 53 (7): 1153–5. PMC 1949295. PMID 17872810. 
  79. ^ Kaufman, David Myland; Heinonen, Olli P.; Slone, Dennis; Shapiro, Samuel (1977). Birth defects and drugs in pregnancy. Littleton, Mass: Publishing Sciences Group. ISBN 0-88416-034-3. OCLC 2387745. [page needed]
  80. ^ Yaffe, Sumner J.; Briggs, Gerald G.; Freeman, Roger Anthony (2005). Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-5651-0. [page needed]
  81. ^ a b c d Characterization of Methylphenidate Exposures Reported to a Regional Poison Control Center – 2000, White & Yadao: Paediatrics & Adolescent Medicine
  82. ^ a b c Annual report 2010, American Association of Poison Control Centers Toxic Exposure Surveillance System – Bronstein et al, Table 22B p.136
  83. ^ a b c d Scharman EJ, Erdman AR, Cobaugh DJ, Olson KR, Woolf AD, Caravati EM, Chyka PA, Booze LL, Manoguerra AS, Nelson LS, Christianson G, Troutman WG (2007). "Methylphenidate poisoning: an evidence-based consensus guideline for out-of-hospital management". Clinical Toxicology 45 (7): 737–52. PMID 18058301. doi:10.1080/15563650701665175.  [1]
  84. ^ a b Klein-Schwartz W (2002). "Abuse and toxicity of methylphenidate". Current Opinion in Pediatrics 14 (2): 219–23. PMID 11981294. doi:10.1097/00008480-200204000-00013. 
  85. ^ Seth (5 February 2011). "Erowid Methylphenidate (Ritalin) Vault : Summary of Medical Uses, Seth". Retrieved 12 May 2014. 
  86. ^ a b c 2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System – Table 22B p.652
  87. ^ a b Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets – Bruggisser et al 2011
  88. ^ a b Stern EJ, Frank MS, Schmutz JF, Glenny RW, Schmidt RA, Godwin JD (1994). "Panlobular pulmonary emphysema caused by i.v. injection of methylphenidate (Ritalin): findings on chest radiographs and CT scans". American Journal of Roentgenology 162 (3): 555–560. PMID 8109495. doi:10.2214/ajr.162.3.8109495. 
  89. ^ Safety of therapeutic methylphenidate in adults: a systematic review of the evidence – 2008, Godfrey
  90. ^ a b Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, Dewey SL, Hitzemann R, Gifford AN, Pappas NR (1999). "Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high"". The Journal of Pharmacology and Experimental Therapeutics 288 (1): 14–20. PMID 9862747. 
  91. ^ Volkow ND, Swanson JM (2003). "Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD". The American Journal of Psychiatry 160 (11): 1909–18. PMID 14594733. doi:10.1176/appi.ajp.160.11.1909. 
  92. ^ Morton WA, Stockton GG (2000). "Methylphenidate Abuse and Psychiatric Side Effects". Primary Care Companion Journal of Clinical Psychiatry 2 (5): 159–64. PMC 181133. PMID 15014637. doi:10.4088/PCC.v02n0502. 
  93. ^ Arria AM, Wish ED (2006). "Nonmedical use of prescription stimulants among students". Pediatric Annals 35 (8): 565–71. PMC 3168781. PMID 16986451. doi:10.3928/0090-4481-20060801-09. 
  94. ^ Harris J (2009). "Is it acceptable for people to take methylphenidate to enhance performance? Yes". BMJ 338: b1955. PMID 19541705. doi:10.1136/bmj.b1955. 
  95. ^ Chatterjee A (2009). "Is it acceptable for people to take methylphenidate to enhance performance? No". BMJ 338: b1956. PMID 19541706. doi:10.1136/bmj.b1956. 
  96. ^ "Ritalin backed as brain-booster". BBC News. 19 June 2009. Retrieved 21 February 2010. 
  97. ^ Davies, Caroline (21 February 2010). "Universities told to consider dope tests as student use of 'smart drugs' soars". The Observer (London). Retrieved 21 February 2010. 
  98. ^ a b c Heal DJ, Pierce DM (2006). "Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system". CNS Drugs 20 (9): 713–38. PMID 16953648. doi:10.2165/00023210-200620090-00002. 
  99. ^ Iversen L (2006). "Neurotransmitter transporters and their impact on the development of psychopharmacology". British Journal of Pharmacology 147 (Suppl 1): S82–8. PMC 1760736. PMID 16402124. doi:10.1038/sj.bjp.0706428. 
  100. ^ Viggiano D, Vallone D, Sadile A (2004). "Dysfunctions in dopamine systems and ADHD: evidence from animals and modeling". Neural Plasticity 11 (1–2): 102, 106–107. PMC 2565441. PMID 15303308. doi:10.1155/NP.2004.97. Full-text [2]
  101. ^ Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–76. PMC 3005101. PMID 21073468. doi:10.1111/j.1471-4159.2010.07109.x. 
  102. ^ Novartis:Focalin XR Overview
  103. ^ Focalin XR – Full Prescribing Information. Novartis.
  104. ^ Concerta XL 18 mg – 36 mg prolonged release tablets last updated on the eMC: 5 November 2010
  105. ^ Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R (2006). "A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study". J Child Adolesc Psychopharmacol 16 (6): 687–98. PMID 17201613. doi:10.1089/cap.2006.16.687. 
  106. ^ Markowitz, J. S., DeVane, C. L., Ramamoorthy, S., & Zhu, H. J. (2009). The psychostimulant d-threo-(R, R)-methylphenidate binds as an agonist to the 5HT1A receptor. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 64(2), 123–125.
  107. ^ Volz TJ (2008). "Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate". Current Neuropharmacology 6 (4): 379–385. PMC 2701286. PMID 19587858. doi:10.2174/157015908787386041. 
  108. ^ Zhang CL, Feng ZJ, Liu Y, Ji XH, Peng JY, Zhang XH, Zhen XC, Li BM (2012). "Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action". PLoS ONE 7 (12): e51910. PMC 3527396. PMID 23284812. doi:10.1371/journal.pone.0051910. 
  109. ^ Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 15 November 2013. 
  110. ^ Kimko HC, Cross JT, Abernethy DR (1999). "Pharmacokinetics and Clinical Effectiveness of Methylphenidate". Clinical Pharmacokinetics 37 (6): 457–70. PMID 10628897. doi:10.2165/00003088-199937060-00002. 
  111. ^ Kimko HC, Cross JT, Abernethy DR (1999). "Pharmacokinetics and clinical effectiveness of methylphenidate". Clin Pharmacokinet 37 (6): 457–70. PMID 10628897. doi:10.2165/00003088-199937060-00002. 
  112. ^ Chan YP, Swanson JM, Soldin SS, Thiessen JJ, Macleod SM, Logan W (1983). "Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid". Pediatrics 72 (1): 56–59. PMID 6866592. 
  113. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 1091–93.
  114. ^ Froimowitz M, Patrick KS, Cody V (1995). "Conformational analysis of methylphenidate and its structural relationship to other dopamine reuptake blockers such as CFT". Pharmaceutical Research 12 (10): 1430–4. PMID 8584475. doi:10.1023/A:1016262815984. 
  115. ^ Prashad M (2001). "Approaches to the Preparation of Enantiomerically Pure (2R,2′R)-(+)-threo-Methylphenidate Hydrochloride" (PDF). Adv. Synth. Catal 343 (5): 379–92. doi:10.1002/1615-4169(200107)343:5<379::AID-ADSC379>3.0.CO;2-4. 
  116. ^ Axten JM, Krim L, Kung HF, Winkler JD (1998). "A Stereoselective Synthesis ofdl-threo-Methylphenidate: Preparation and Biological Evaluation of Novel Analogues". The Journal of Organic Chemistry 63 (26): 9628. doi:10.1021/jo982214t. 
  117. ^ Singh S (2000). "Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists" (PDF). Chem. Rev. 100 (3): 925–1024 (1008). PMID 11749256. doi:10.1021/cr9700538. 
  118. ^ a b Moses, Scott (26 July 2009). "Methylphenidate". Family Practice Notebook. Retrieved 7 August 2012. 
  119. ^ "Education/Training » Clinical Resources". Illinois DocAssist website. University of Illinois at Chicago. Retrieved 26 July 2012. Ritalin‑SR, methylphenidate SR, Methylin ER, and Metadate ER are the same formulation and have the same drug delivery system 
  120. ^ "Apo‑Methylphenidate SR product monograph" (PDF). Apotex Inc. 31 March 2005. "Comparative Bioavailability" section. Retrieved 26 July 2012.  If the monograph link doesn't work, visit Health Canada's Drug Product Database query form one time, then click the monograph link again.
  121. ^ "New product: Sandoz Methylphenidate SR 20 mg" (PDF). Sandoz Canada Inc. 5 May 2009. Retrieved 26 July 2012. An alternative to Ritalin‑SR from Novartis 
  122. ^ Concerta for Kids with ADHD. (1 April 2003). Retrieved on 30 April 2011.
  123. ^ Concerta (Methylphenidate Extended-Release Tablets) Drug Information: User Reviews, Side Effects, Drug Interactions and Dosage at RxList. Retrieved on 30 April 2011.
  124. ^ Ritalin LA® (methylphenidate hydrochloride) extended-release capsules, Novartis
  125. ^ Metadate CD. Retrieved on 30 April 2011.
  126. ^ [3] Quillivant PI Sheet. Retrieved 13 October 2014.
  127. ^ Panizzon L (1944). "La preparazione di piridile piperidil-arilacetonitrili e di alcuni prodotti di trasformazione (Parte Ia)". Helvetica Chimica Acta 27: 1748–56. doi:10.1002/hlca.194402701222. 
  128. ^ Meier R, Gross F, Tripod J (1954). "Ritalin, a new synthetic compound with specific analeptic components". Klinische Wochenschrift 32 (19–20): 445–50. PMID 13164273. doi:10.1007/BF01466968. 
  129. ^ a b Myers, Richard L (August 2007). The 100 most important chemical compounds: a reference guide By Richard L. Myers. ISBN 978-0-313-33758-1. Retrieved 10 September 2010. 
  130. ^ Leandro Panizzon et al Pyridine and piperdjine compounds U.S. Patent 2,507,631 Issue date: 16 May 1950
  131. ^ Rudolf Rouietscji et al Process for the conversion of U.S. Patent 2,838,519 Issue date: 10 June 1958
  132. ^ Rudolf Rouietscji et alProcess for the conversion of U.S. Patent 2,957,880 Issue date: 25 October 1960
  133. ^ Stolerman, Ian (2010). Encyclopedia of psychopharmacology. Berlin London: Springer. p. 763. ISBN 3540686983. 
  134. ^ Ritalin and Attention Deficit Disorder: History of its Use, Effects and Side Effects. Susan McCrossin, 1995;
  135. ^ Bradley, Charles. Benzedrine® and Dexedrine® in the Treatment of Children's Behavior Disorders. Pediatrics 1950; 5:1 24–37
  136. ^ Terrance Woodworth (16 May 2000). "DEA Congressional Testimony". Retrieved 2 November 2007. 
  137. ^ Approved Drug Therapies (637) Concerta, Alza. CenterWatch. Retrieved on 30 April 2011.
  138. ^ Green List: Annex to the annual statistical report on psychotropic substances (form P) PDF (1.63 MB) 23rd edition. August 2003. International Narcotics Board, Vienna International Centre. Retrieved 2 March 2006.
  139. ^ "Misuse of Drugs Act 1971 (c. 38): SCHEDULE 2: Controlled Drugs". Office of Public Sector Information. Retrieved 15 June 2009. 
  140. ^ "Narkotikastrafflag (1968:64)". Ministry of Justice. Retrieved 15 January 2014. 
  141. ^ Frances C, Hoizey G, Millart H, Trenque (2004). "Paediatric methylphenidate (Ritalin) restrictive conditions of prescription in France". British Journal of Clinical Pharmacology 57 (1): 115–6. PMID 14678352. doi:10.1046/j.1365-2125.2003.01943.x. 
  142. ^ Lakhan SE, Hagger-Johnson GE (2007). "The impact of prescribed psychotropics on youth". Clin Pract Epidemol Ment Health 3 (1): 21. PMC 2100041. PMID 17949504. doi:10.1186/1745-0179-3-21. 
  143. ^ New Research Helps Explain Ritalin's Low Abuse Potential When Taken As Prescribed – 09/29/1998. Retrieved on 30 April 2011.
  144. ^ Stimulant ADHD Medications: Methylphenidate and Amphetamines – InfoFacts – NIDA. Retrieved on 30 April 2011.
  145. ^ Agay, Nirit; Yechiam, Eldad; Carmel, Ziv; Levkovitz, Yechiel; (22 July 2010). "Non-specific effects of Methylphenidate (Ritalin) on cognitive ability and decision-making of ADHD and healthy adults.". Psychopharmacology 210 (4): 511–519. doi:10.1007/s00213-010-1853-4. 
  146. ^ Ouellette EM (1991). "Legal issues in the treatment of children with attention deficit hyperactivity disorder". Journal of Child Neurology. 6 Suppl: S68–75. PMID 2002217. 
  147. ^ FDA OKs Concerta for Adult ADHD,
  148. ^ NICE – Can methylphenidate be used for adults with attention deficit hyperactivity disorder (ADHD)? (4 July 2013). Retrieved on 5 December 2013.
  149. ^ Ritalin for Adults. (6 March 2007). Retrieved on 30 April 2011.
  150. ^ Drug Enforcement Administration, Greene, S.H., Response to CHADD petition concerning Ritalin, 1995, 7 August. Washington, DC: DEA, U.S. Department of Justice.
  151. ^ The Neurobiology of ADHD,
  152. ^ L. ALAN SROUFE (28 January 2012). "Ritalin Gone Wrong – Opinion – Children\'s A.D.D.Drugs Don\'t Work Long-Term". The New York Times. Archived from the original on 3 February 2012. Retrieved 3 February 2012. (Archived by WebCite® at [4]) 
  153. ^

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