Unifiram

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Unifiram
Skeletal formula
Ball-and-stick model of unifiram
Clinical data
Other namesDM-232
Legal status
Legal status
  • In general: unscheduled
Identifiers
  • 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)
  • C2CN1C(=O)CCC1CN2S(=O)(=O)c(cc3)ccc3F
  • 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
 ☒NcheckY (what is this?)  (verify)

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]

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

References

  1. ^ Galeotti N, Ghelardini C, Pittaluga A, Pugliese AM, Bartolini A, Manetti D, et al. (December 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 MN, Bucherelli C, Baldi E, Bartolini A (June 2002). "DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer". 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. ^ a b c d 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 Reviews. 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, et al. (January 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, et al. (February 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, et al. (December 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, et al. (September 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. ^ a b c d Gualtieri F (2016). "Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings". Journal of Enzyme Inhibition and Medicinal Chemistry. 31 (2): 187–194. doi:10.3109/14756366.2015.1021252. PMID 25831025. S2CID 207528957.
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