Some neurochemical properties of pramiracetam (CI‐879), a new cognition‐enhancing agent
Abstract
The present study was initiated to examine the effect of pramiracetam sulfate [N‐[2‐[bis(1‐methylethyl)amino]ethyl]‐2 oxo‐1‐pyrrolidineacetamide sulfate (1:1)] (PR), a new cognition‐activator agent, on various neurochemical parameters in order to gain some insight into the mechanism of action of this agent. PR (100 mg/kg i.p.) did not alter the concentration of norepinephrine, dopamine (DA), serotonin (5‐HT), 5‐hydroxyindoleacetic, and homovanillic acid in various brain areas. The agent also did not alter d‐methamphetamine‐induced changes in monoamine metabolism nor prolactin concentration in rat serum. PR did not exhibit any affinity in vitro for dopaminergic, adrenergic, serotoninergic, GABAergic, muscarinic, adenosine (IC50 > 10 μM), and benzodiazepine receptors (IC50 > 1 μM) binding sites. It may be concluded that the mechanism of action of pramiracetam does not appear to be due to a direct action upon DA and 5‐HT neurotransmitter systems or various brain receptors. PR (44 and 88 mg/kg i.p.) caused a significant increase in the rate of sodium‐dependent high‐affinity choline uptake (HACU) into rat hippocampal synptosomes in vitro. This was specific as no effect was observed in cerebral cortex and corpus striatum. These results would seem to indicate that PR is accelerating hippocampal acetylcholine turnover and thus septal‐hippocampal cholinergic neuronal impulse flow. This effect could be at least partially responsible for the enhancement of cognition processes observed for this agent.
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