Involvement of the cholinergic system in the effects of nefiracetam (DM-9384) on carbon monoxide (CO)-induced acute and delayed amnesia.

Abstract

The effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide (DM-9384, nefiracetam), a cyclic derivative of GABA, were investigated in the carbon monoxide (CO)-induced amnesia model in mice using the passive avoidance task. Memory deficiency occurred when mice were exposed to CO before memory was completely consolidated after training (acute amnesia), at 7 days before training and 7 days after training (delayed amnesia). DM-9384 prolonged the step-down latency in mice with CO-induced amnesia. Scopolamine blocked the anti-amnesic effect of DM-9384 on delayed amnesia that had been induced by pre- or post-training exposure to CO. Bicuculline had a tendency to antagonize the anti-amnesic effect of DM-9384, but this tendency was not significant. Under these conditions, no significant change in the activity of choline acetyltransferase and glutamic acid decarboxylase was observed in the frontal cortex, striatum and hippocampus. These results suggest that DM-9384 potentiates cholinergic neuronal function and that it may modify acquisition and/or consolidation of memory.

• Authors: M Hiramatsu, T Koide, S Ishihara, T Shiotani, T Kameyama, T Nabeshima
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 216 Issue 2 Pg. 279-85 (Jun 05 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1397012 (Publication Type: Journal Article)

Chemical References

• Central Nervous System Agents
• Pyrrolidinones
• nefiracetam
• Carbon Monoxide
• Choline O-Acetyltransferase
• Glutamate Decarboxylase

Topics

• Amnesia (chemically induced, drug therapy)
• Animals
• Avoidance Learning (drug effects)
• Carbon Monoxide (toxicity)
• Central Nervous System Agents (pharmacology)
• Cerebral Cortex (enzymology)
• Choline O-Acetyltransferase (metabolism)
• Cholinergic Fibers (drug effects, enzymology, physiology)
• Corpus Striatum (enzymology)
• Glutamate Decarboxylase (metabolism)
• Hippocampus (enzymology)
• Male
• Mice
• Mice, Inbred Strains
• Pyrrolidinones (pharmacology)