Sunifiram

Last Updated: September 28 2022

Sunifiram (DM-235) is an AMPAkine drug (acting via AMPA receptors) that exerts anti-amnesiac properties. With similar actions as nefiracetam, it holds promise as a cognitive enhancer but is relatively understudied currently.

Sunifiram is most often used for

Summary

Sunifiram (DM-235) is a synthetic derivative of piracetam, although due to breaking the pyrrolidone backbone it is no longer in the racetam class of drugs (yet by being derived from them, it is still commonly associated with this class).

Sunifiram has mechanisms similar to nefiracetam in the hippocampus, and similar to that drug sunifiram shows anti-amnesiac properties and is potentially a cognitive enhancer. Its anti-amnesiac activity is several orders of magnitude greater than piracetam on a per weight basis, and preliminary evidence suggest it has a similarly low toxicity profile.

This compound is known as an AMPAkine due to exerting most of its actions via the AMPA receptor (one of the three main subsets of glutamate receptors, alongside NDMA and kainate). This enhancement of AMPA function seems to also rely on enhancing signalling via the glycine binding site of NMDA receptors, although one minimal signalling goes through the NMDA receptor then the benefits on AMPA receptors seem dose-dependent.

What else is Sunifiram known as?
Note that Sunifiram is also known as:
  • DM-235
Dosage information

It is very hard to determine an optimal dose for sunifiram due to such limited evidence, but since 1mg/kg has been determined to be good for both mice and rats this gives a preliminary human dose of 0.08-0.16mg/kg (for a 150lb person, 5.4-11mg).

It is not clear if higher doses are better.

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References
2.^Martini E, Salvicchi A, Ghelardini C, Manetti D, Dei S, Guandalini L, Martelli C, Melchiorre M, Cellai C, Scapecchi S, Teodori E, Romanelli MNDesign, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancersBioorg Med Chem.(2009 Nov 1)
3.^Martini E, Ghelardini C, Dei S, Guandalini L, Manetti D, Melchiorre M, Norcini M, Scapecchi S, Teodori E, Romanelli MNDesign, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancersBioorg Med Chem.(2008 Feb 1)
4.^Manetti D, Ghelardini C, Bartolini A, Dei S, Galeotti N, Gualtieri F, Romanelli MN, Teodori EMolecular simplification of 1,4-diazabicyclo{4.3.0}nonan-9-ones gives piperazine derivatives that maintain high nootropic activityJ Med Chem.(2000 Nov 16)
5.^Scapecchi S, Martelli C, Ghelardini C, Guandalini L, Martini E, Gualtieri F2-pyrrolidinone moiety is not critical for the cognition-enhancing activity of piracetam-like drugsFarmaco.(2003 Sep)
7.^Galeotti N, Ghelardini C, Pittaluga A, Pugliese AM, Bartolini A, Manetti D, Romanelli MN, Gualtieri FAMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram)Naunyn Schmiedebergs Arch Pharmacol.(2003 Dec)
9.^Ghelardini C, Galeotti N, Gualtieri F, Romanelli MN, Bucherelli C, Baldi E, Bartolini ADM235 (sunifiram): a novel nootropic with potential as a cognitive enhancerNaunyn Schmiedebergs Arch Pharmacol.(2002 Jun)
10.^Shioda N, Yamamoto Y, Han F, Moriguchi S, Yamaguchi Y, Hino M, Fukunaga KA novel cognitive enhancer, ZSET1446/ST101, promotes hippocampal neurogenesis and ameliorates depressive behavior in olfactory bulbectomized miceJ Pharmacol Exp Ther.(2010 Apr)