A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission.
GRIs may be used in the clinical treatment of seizures, convulsions, or epilepsy as anticonvulsants or antiepileptics, anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), and panic disorder (PD) as anxiolytics, insomnia as hypnotics, muscle tremors or spasms as muscle relaxants, and chronic pain as analgesics. They may also potentially be used as anesthetics in surgery.
GRIs can induce a wide range of psychological and physiological effects, including a general and subjective alteration in consciousness, dizziness, blurry vision, diplopia or double vision, nystagmus or involuntary eye movements, amblyopia or "lazy eye", tinnitus or "ear ringing", sedation, drowsiness or somnolence, narcolepsy, tiredness or weakness, fatigue or lethargy, aches and pains, headache, nausea and vomiting, gastrointestinal disturbances, shakiness, disorientation, diminished awareness, impaired attention, focus, and concentration, decreased drive and motivation, stuttering and slurring of speech, confusion, cognitive and memory impairment, mood lift or drop, depression, anxiolysis, disinhibition, stress reduction, euphoria or dysphoria, irritability, aggression, anger or rage, increased appetite and subsequent weight gain, ataxia or impaired coordination and balance, muscle relaxation, trembling or muscle tremors and spasms, paresthesia or "pins and needles", analgesia, respiratory depression, and dyspnea or shortness of breath, among others.
However, many of these properties are dependent on whether the GRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce peripheral effects.
At very high doses characterized by overdose, a number of symptoms may come to prominence, including severe cognitive deficit to the point of acute retardation, anterograde or retrograde amnesia, drooling, piloerection or "goose bumps", agitation or restlessness, flailing, thrashing, and screaming, unintentional or accidental injury, delirium, hallucinations, myoclonus, dystonia, paralysis, stupor, faintness or loss of consciousness, seizures or convulsions, status epilepticus, coma, and respiratory arrest or cessation of breathing, potentially resulting in hospitalization, brain damage, and/or death.
List of GRIs
- ^ a b c d Borden LA, Murali Dhar TG, Smith KE, Weinshank RL, Branchek TA, Gluchowski C. (1994). "Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1.". Eur J Pharmacol. 269 (2): 219–224. PMID 7851497. doi:10.1016/0922-4106(94)90089-2.
- PAMs (abridged; see here for a full list): α-EMTBL
- Alcohols (e.g., ethanol)
- Avermectins (e.g., ivermectin)
- Barbiturates (e.g., phenobarbital)
- Benzodiazepines (e.g., diazepam)
- Bromide compounds (e.g., potassium bromide)
- Carbamates (e.g., meprobamate)
- Dihydroergolines (e.g., ergoloid (dihydroergotoxine))
- Fenamates (e.g., mefenamic acid)
- Flavonoids (e.g., apigenin, hispidulin)
- Imidazoles (e.g., etomidate)
- Kava constituents (e.g., kavain)
- Neuroactive steroids (e.g., allopregnanolone, cholesterol)
- Nicotinamide (niacinamide)
- Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil), cyclopyrrolones (e.g., zopiclone), imidazopyridines (e.g., zolpidem), pyrazolopyrimidines (e.g., zaleplon))
- Phenols (e.g., propofol)
- Piperidinediones (e.g., glutethimide)
- Pyrazolopyridines (e.g., etazolate)
- Quinazolinones (e.g., methaqualone)
- Retigabine (ezogabine)
- Skullcap constituents (e.g., baicalin)
- Sulfonylalkanes (e.g., sulfonmethane (sulfonal))
- Valerian constituents (e.g., valerenic acid)
- Volatiles/gases (e.g., chloral hydrate, chloroform, diethyl ether, paraldehyde, sevoflurane)
- NAMs: 1,3M1B
- α5IA (LS-193,268)
- β-Lactams (e.g., penicillins, cephalosporins, carbapenems)
- FG-7142 (ZK-31906)
- Fiproles (e.g., fipronil)
- Flavonoids (e.g., amentoflavone, oroxylin A)
- Fluoroquinolones (e.g., ciprofloxacin)
- Iomazenil (123I)
- Isopregnanolone (sepranolone)
- Pentetrazol (metrazol)
- Picrotoxin (i.e., picrotin and picrotoxinin)
- Pregnenolone sulfate
- Ro 15-4513
- Ro 19-4603