(8aR)-2-[(4-fluorophenyl)sulfonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one, (CAS Number) 272786-64-8, (PubChem) CID 9861054, (ChemSpider) 8036753, (ChEMBL) CHEMBL140717, C13H15FN2O3S, DM232
In the few studies done, the most common dose was .1mg/kg in both mice and rats and was found to be anti-amnesic in the water maze test [1,6]; this dose works out to roughly 2mg in an adult human (70kgs). One study also used 1mg/kg in rats and found it to have anti-amnesic effects in rats; this dose would be ~17mg for a healthy adult human (70kgs) .
Unifiram (DM-232) is another recent entrant in the Racetam family (think piracetam) which is structurally similar to an ampakine and is closely related to Sunifiram (DM-235), with the first studies on the drug being published in 2003. More studies need to be conducted to fully elucidate the effects of Unifiram, but it appears to be effective as a Nootropic and as an anti-amnesic.
Unifiram Mechanism of Action
Based on the studies conducted, both in vivo and in vitro, Unifiram reverses the effects of AMPA antagonists, NMDA antagonists, and muscarinic antagonists, which would imply the underlying mechanisms of action. One study found that Unifiram reversed the effects of both AMPA antagonists and NMDA antagonists, both of which mimic glutamate, and are directly correlated to learning and memory .
Two studies noted that Unifiram increased the release of acetylcholine in rats, and a third study showed Unifiram negated the effects of scopolamine [3.4.6]; at first glance, these two facts may not seem to be related, but it turns out scopolamine is a muscarinic antagonist specifically affecting the M1 receptor. Reducing the effect of a muscarinic antagonist could be the explanation for the noted increase in acetylcholine release, as the M1 muscarinic receptor is a cholinergic receptor. The effect causing Unifiram to inhibit the negative effects of muscarinic antagonism is most likely the same cause for the increase in acetylcholine.
In the studies conducted, Unifiram was noted to have three primary benefits: anti-amnesia, acetylcholine agonism, and anti-sedative and anti-hypnotic effects. Two of the studies on Unifiram and its analogs focused on its ability to reverse the amnesic effects of AMPA antagonists and its precognitive effects utilizing the Mouse Passive Avoidance test for their experimental methodology [1,2]. Another study noted that Unifiram appears to increase acetylcholine release in rats; acetylcholine is very strongly correlated to memory and learning . There was one other study done that found, on top of being an anti-amnesic, Unifiram reduces the effects of barbiturates especially the effects of hypnosis and sedation .
At the dose of 1mg/kg, the highest dose tested so far, it was found that Unifiram showed no toxicity and had no negative effects on motor coordination. This would suggest that a dose of .29mg/kg in an adult human should have no negative effects, and should be non-toxic .