Sunifiram
Chemical compound
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Other names | DM-235 |
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Formula | C 14 H 18 N 2 O 2 |
Molar mass | 246.310 g·mol −1 |
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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]
Pharmacology
The mechanism of action of sunifiram is unknown. [1] 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. [1] [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. [1] [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 . [1] 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 . [4] [5]
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 (K i = 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. [1]
See also
References
- 1 2 3 4 5 6 7 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 .
- ↑ Manetti D, Ghelardini C, Bartolini A, Dei S, Galeotti N, Gualtieri F, et al. (November 2000). "Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity". Journal of Medicinal Chemistry . 43 (23): 4499–4507. doi : 10.1021/jm000972h . hdl : 2158/307040 . PMID 11087574 .
- 1 2 3 4 5 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 .
- ↑ 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): 942–951. doi : 10.1002/hipo.22150 . PMID 23733502 . S2CID 7894429 .
- ↑ 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 : 150–157. doi : 10.1016/j.bbr.2012.12.054 . PMID 23295391 . S2CID 41376899 .