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Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide

T Nabeshima, K Tohyama, K Murase, S Ishihara, T Kameyama, T Yamasaki, S Hatanaka, H Kojima, T Sakurai and Y Takasu

Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)- acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABAA and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM- 9384 attenuates CXM-induced amnesia by interacting with GA-BAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.

Volume 257, Issue 1, pp. 271-275, 04/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.