Unifiram

Unifiram (developmental code name DM-232) is an experimental drug.[1] that has antiamnesic and other effects in animal studies with far greater potency than piracetam.[2][3] A number of related compounds are known, such as sunifiram (DM-235) and sapunifiram (MN-19).[4][5][6] Unifiram has two enantiomers, with the dextro form being the more active isomer.[7] It has been shown to reduce the duration of hypnosis induced by pentobarbital, without impairing motor coordination.[8] As of 2015, no formal human studies with unifiram have been conducted. Unifiram is not patented and, despite the lack of human and long-term toxicity studies, it is commonly sold online.[9]

Unifiram
Clinical data
Other namesDM-232
Legal status
Legal status
  • In general: unscheduled
Identifiers
IUPAC name
  • 2-[(4-Fluorophenyl)sulfonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H15FN2O3S
Molar mass298.33 g·mol−1
3D model (JSmol)
SMILES
  • C2CN1C(=O)CCC1CN2S(=O)(=O)c(cc3)ccc3F
InChI
  • InChI=1S/C13H15FN2O3S/c14-10-1-4-12(5-2-10)20(18,19)15-7-8-16-11(9-15)3-6-13(16)17/h1-2,4-5,11H,3,6-9H2 N
  • Key:SNRTZFZAFBIBJP-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

Pharmacology

Unifiram, as well as sunifiram, were assayed at a wide panel of sites, including the most important receptors, ion channels, and transporters, but showed no affinity for any of the sites.[9][3] They specifically did not bind to the glutamate, GABA, serotonin, dopamine, adrenergic, histamine, acetylcholine, or opioid receptors at concentrations of up to 1 μM.[9][3] In addition, the drugs were tested on recombinant AMPA receptors and showed no potentiation of the receptors, indicating that they do not act as AMPA receptor positive allosteric modulators.[9] However, they were able to prevent the amnesia induced by the AMPA receptor antagonist NBQX in the passive avoidance test, suggesting that indirect/downstream AMPA receptor activation may be involved in their memory-enhancing effects.[3]

Chemistry
(R)-(+)-unifiram (dextrounifiram).

References
  1. 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. doi:10.1007/s00210-003-0812-6. PMID 14600801. S2CID 11810684.
  2. 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" (PDF). Naunyn-Schmiedeberg's Archives of Pharmacology. 365 (6): 419–426. doi:10.1007/s00210-002-0577-3. hdl:2158/772195. PMID 12070754. S2CID 9501712.
  3. Romanelli MN, 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 Rev. 12 (1): 39–52. doi:10.1111/j.1527-3458.2006.00039.x. PMC 6741768. PMID 16834757.
  4. 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. doi:10.1016/j.bmc.2003.10.025. PMID 14697772.
  5. 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. doi:10.1016/j.bmc.2007.10.050. PMID 17981042.
  6. 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. doi:10.1016/j.bmc.2008.10.017. PMID 18954993.
  7. Martini, E.; Ghelardini, C.; Bertucci, C.; Dei, S.; Gualtieri, F.; Guandalini, L.; Manetti, D.; Scapecchi, S.; Teodori, E.; Romanelli, M. N. (2005). "Enantioselective synthesis and preliminary pharmacological evaluation of the enantiomers of unifiram (DM232), a potent cognition-enhancing agent". Medicinal Chemistry. 1 (5): 473–480. doi:10.2174/1573406054864142. PMID 16787332.
  8. Ghelardini, C.; Galeotti, N.; Gualtieri, F.; Manetti, D.; Bucherelli, C.; Baldi, E.; Bartolini, A. (2002). "The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats". Drug Development Research. 56: 23–32. doi:10.1002/ddr.10055. hdl:2158/772162. S2CID 85091757.
  9. Gualtieri F (2016). "Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings". J Enzyme Inhib Med Chem. 31 (2): 187–94. doi:10.3109/14756366.2015.1021252. PMID 25831025. S2CID 207528957.
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