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(RS)-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide, (CAS Number) 62613-82-5, (ATC Code) N06BX07, (PubChem) CID 4626, (ChemSpider) 4465, (UNII) P7U817352G, (KEGG) D07346, (ChEMBL) CHEMBL36633, (Formula) C6H10N2O3
Of the studies consulted, most used both 3mg/kg and 30mg/kg (with the max using 100mg/kg) in adult rats and mice to reduce the effect of drug-induced amnesia, and doses up to 100mg/kg were shown to be effective [3,4,5,10]. Taking into account Allometric Scaling for an average sized human, the dose would be 29.072mg/kg or 2035mg for a 70kg (154lbs) person; all doses referred to are on a daily schedule.
Oxiracetam is a derivative of piracetam. The earliest study done on Oxiracetam was published in 1990, and since then it has been shown to have positive effects on various aspects of cognition; some of the positive effects noted are preventing memory deficits induced by 2 different drugs, potentially improving spatial memory and spatial learning, and potentially increasing cellular ATP. While the exact mechanism of action for Oxiracetam is still unknown, or unproven, it has found usage in the treatment of mild to moderate dementia, and use by the Nootropic community in improving memory and general cognition.
Oxiracetam’s Mechanism of Action
No officially accepted mechanism of action has been identified, although it is believed Oxiracetam affects the potentiation of neurotransmitters through voltage-gated ion channels . Another study showed Oxiracetam increased membrane-bound PKC; this may lend credence to the theory of Oxiracetam effecting voltage-gated ion channels, as PKC is activated by increases in Ca2+ . The final posited theory on Oxiracetam’s mechanism of action is it acts upon NMDA receptors ; NMDA receptors are very closely linked to both memory and plasticity, which would also indicate Oxiracetam is glutamatergic. Of note, when NMDA receptors are agonized, ion channels (specifically NA+ and Ca2+ ion channels), which lends further credence to the original theory posited on Oxiracetam’s mechanism of action.
Over the last few decades, Oxiracetam has been shown to have many positive effects on various aspects of cognition, most of which are directly related to memory. The first noted benefit of Oxiracetam is in preventing memory deficits induced by the drug MK-801. Adult mice were given .15mg/kg of MK-801 and then tested using the elevated plus-maze test; those mice treated with both 3 and 30mg/kg of Oxiracetam showed no signs of memory impairment that would normally be induced by MK-801 . Another study conducted on adult mice, utilizing the elevated plus-maze test, showed that Oxiracetam attenuates the effects of Scopolamine induced amnesia on spatial memory but has no effects on memory impairment induced by Diazepam; the authors theorized this was related to the anxiolytic nature of Diazepam .
Another aspect of cognition that Oxiracetam has been shown to positively affect is social recognition (of conspecifics in rats). Normally, when an adult rat is treated with the drug Trimethyltin, they experience impairment in social recognition due to its neurotoxicity, but when treated with Oxiracetam for seven days prior to Trimethyltin dosing, the rats did not experience the social recognition impairment. This would suggest that longer term dosing of Oxiracetam could attenuate the effects of neurotoxicity of other drugs .
When astrocytes which had been cultured in vitro and were subsequently treated with Oxiracetam for two weeks, they exhibited increased adenosine triphosphate (ATP); the authors theorized this is directly tied to the general cognitive improvements seen by dementia patients who had been treated with Oxiracetam . There is further need to study this aspect in both an in vitro and in vivo capacity to determine its exact effect on humans, and what role it plays in Oxiracetam’s ability to alleviate dementia symptoms .
Mice (which had been bred for a trait that impaired learning ability) were treated with 50mg/kg Oxiracetam and subjected to the Morris Water Maze task, during this procedure, they were tested on two key capabilities; the first test was to determine how, or if, Oxiracetam affected motor skills in mice and the other capability tested was spatial learning. It was found that learning impaired mice treated with Oxiracetam had significant improvements in spatial learning ability without having any positive or negative affect on their motor skills .
Another study conducted on both adult rats and mice compared the effects of Piracetam and Oxiracetam on acquisition performance, step-down retention, and electroshock-induced amnesia. It was found that Piracetam and Oxiracetam were equal in treating electroshock-induced amnesia, but Oxiracetam outperformed Piracetam significantly in both step-down retention and acquisition performance .
Of the surveyed studies, none noted any toxicity in levels up to 100mg/kg in adult rats and mice; further studies will need to be conducted to determine at what levels Oxiracetam is safe in adult humans .