Open Access Articles- Top Results for Sunifiram


Systematic (IUPAC) name
Clinical data
314728-85-3 7pxY
PubChem CID 4223812
ChEMBL CHEMBL309176 7pxN
Chemical data
Formula C14H18N2O2
246.304 g/mol
 14pxN (what is this?)  (verify)

Sunifiram (DM-235) is a piperazine derived research chemical which has nootropic effects in animal studies with significantly higher potency than piracetam.[1][2] A number of related compounds are known, including unifiram (DM-232).[3][4][5]

Mechanisms of action

  1. Sunifiram activates AMPA-mediated neurotransmission.[6]
  2. It enhances LTP in a bell-shaped dose–response relationship. This enhancement by sunifiram is associated with an increase in phosphorylation of AMPAR through activation of protein kinase II (CaMKII) and an increase in phosphorylation of NMDAR through activation of protein kinase C α (PKCα). More specifically, sunifiram stimulates the glycine-binding site of NMDAR with concomitant PKCα activation through Src kinase. Enhancement of PKCα activity triggers hippocampal LTP through CaMKII activation.[7]
  3. Sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation.[8] PKC activation may be a common mechanism amongst cognition stimulating drugs from different chemical classes.[9]
  4. Sunifiram aids in the release of acetylcholine in the cerebral cortex.[10]


As of 2014, the safety of sunifiram in humans remains unknown, and no formal studies with it in humans have been conducted.

Mice injected with sunifiram at 1mg/kg of body weight, i.e. 1,000 times the minimal effective dose required to prevent scopolamine-induced amnesia, did not exhibit any collateral symptoms.[10] This, however, does not address long-term safety or drug interactions.

Activation of PKC-α[7] by sunifiram may present safety concerns of its own.


  1. ^ Ghelardini, C.; Galeotti, N.; Gualtieri, F.; Romanelli, M.; Bucherelli, C.; Baldi, E.; Bartolini, A. (2002). "DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer". Naunyn-Schmiedeberg's archives of pharmacology 365 (6): 419–426. PMID 12070754. doi:10.1007/s00210-002-0577-3.  edit
  2. ^ Romanelli, M.; Galeotti, N.; Ghelardini, C.; Manetti, D.; Martini, E.; Gualtieri, F. (2006). "Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers". CNS Drug Reviews 12 (1): 39–52. PMID 16834757. doi:10.1111/j.1527-3458.2006.00039.x.  edit
  3. ^ Scapecchi, S.; Martini, E.; Manetti, D.; Ghelardini, C.; Martelli, C.; Dei, S.; Galeotti, N.; Guandalini, L.; Novella Romanelli, M.; Teodori, E. (2004). "Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs". Bioorganic & Medicinal Chemistry 12 (1): 71–85. PMID 14697772. doi:10.1016/j.bmc.2003.10.025.  edit
  4. ^ Martini, E.; Ghelardini, C.; Dei, S.; Guandalini, L.; Manetti, D.; Melchiorre, M.; Norcini, M.; Scapecchi, S.; Teodori, E.; Romanelli, M. N. (2008). "Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers". Bioorganic & Medicinal Chemistry 16 (3): 1431–1443. PMID 17981042. doi:10.1016/j.bmc.2007.10.050.  edit
  5. ^ Martini, E.; Norcini, M.; Ghelardini, C.; Manetti, D.; Dei, S.; Guandalini, L.; Melchiorre, M.; Pagella, S.; Scapecchi, S.; Teodoria, E. (2008). "Design, synthesis and preliminary pharmacological evaluation of new analogues of DM232 (unifiram) and DM235 (sunifiram) as cognition modulators". Bioorganic & Medicinal Chemistry 16 (23): 10034–10042. PMID 18954993. doi:10.1016/j.bmc.2008.10.017.  edit
  6. ^ Galeotti, N.; Ghelardini, C.; Pittaluga, A.; Pugliese, A.; Bartolini, A.; Manetti, D.; Romanelli, M.; Gualtieri, F. (2003). "AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram)". Naunyn-Schmiedeberg's archives of pharmacology 368 (6): 538–545. PMID 14600801. doi:10.1007/s00210-003-0812-6.  edit
  7. ^ a b Moriguchi, S.; Tanaka, T.; Narahashi, T.; Fukunaga, K. (2013). "Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine binding site of N-methyl-D-aspartate receptor". Hippocampus 23: 942–951. PMID 23733502. doi:10.1002/hipo.22150.  edit
  8. ^ Moriguchi, S.; Tanaka, T.; Tagashira, H.; Narahashi, T.; Fukunaga, K. (2013). "Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice". Behavioural Brain Research 242: 150–157. PMID 23295391. doi:10.1016/j.bbr.2012.12.054.  edit
  9. ^ Lucchi, L.; Pascale, A.; Battaini, F.; Govoni, S.; Trabucchi, M. (1993). "Cognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult rats". Life sciences 53 (24): 1821–1832. PMID 8246681. doi:10.1016/0024-3205(93)90490-T.  edit
  10. ^ a b Manetti, D.; Ghelardini, C.; Bartolini, A.; Dei, S.; Galeotti, N.; Gualtieri, F.; Romanelli, M. N.; Teodori, E. (2000). "Molecular simplification of 1,4-diazabicyclo4.3.0nonan-9-ones gives piperazine derivatives that maintain high nootropic activity". Journal of medicinal chemistry 43 (23): 4499–4507. PMID 11087574. doi:10.1021/jm000972h.  edit