Sunifiram

Sunifiram (developmental code name DM-235) is an experimental drug which has antiamnesic effects in animal studies and with significantly higher potency than piracetam.[1] Sunifiram is a molecular simplification of unifiram (DM-232).[2] Another analogue is sapunifiram (MN-19).[3] As of 2016, sunifiram had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world.[1]

Sunifiram
Clinical data
Other namesDM-235
Legal status
Legal status
  • US: Not FDA approved; unscheduled
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H18N2O2
Molar mass246.310 g·mol−1
3D model (JSmol)
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Pharmacology

The mechanism of action of sunifiram is unknown.[4] Sunifiram, as well as unifiram, 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.[4][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.[4][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.[4] 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] It is reported that sunifiram stimulates CaMKII and PKCα pathways, and that this action depends on the activation of glycine site of NMDA receptors.[5][6]

Sunifiram, as well as other nootropics such as piracetam, levetiracetam, and aniracetam are able to antagonize inhibition of glucose transport by barbiturates (e.g., pentobarbital), diazepam, and certain other drugs in human erythrocytes in vitro (Ki = 26.0 uM for sunifiram), and this action has been found to correlate with their potency in reversing scopolamine-induced memory deficits in mice.[3] However, this action has been regarded as very unlikely to represent the main mechanism of action of sunifiram.[4]

See also

References
  1. 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): 187–94. doi:10.3109/14756366.2015.1021252. PMID 25831025.
  2. 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" (PDF). Journal of Medicinal Chemistry. 43 (23): 4499–4507. doi:10.1021/jm000972h. hdl:2158/307040. PMID 11087574.
  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. 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): 187–94. doi:10.3109/14756366.2015.1021252. PMID 25831025.
  5. Moriguchi S, Tanaka T, Narahashi T, Fukunaga K (October 2013). "Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor". Hippocampus. 23 (10): 942–51. doi:10.1002/hipo.22150. PMID 23733502.
  6. Moriguchi S, Tanaka T, Tagashira H, Narahashi T, Fukunaga K (April 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: 150–7. doi:10.1016/j.bbr.2012.12.054. PMID 23295391.
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