Unifiram

Last updated
Unifiram
Unifiram.svg
Unifiram molecule ball.png
Clinical data
Other namesDM-232
Legal status
Legal status
  • In general: unscheduled
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C13H15FN2O3S
Molar mass 298.33 g·mol−1
3D model (JSmol)
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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]

Contents

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

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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.
  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.
  3. 1 2 3 4 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 .
  9. 1 2 3 4 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.
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