Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide
Nabeshima, T.; Tohyama, K.; Murase, K.; Ishihara, S.; Kameyama, T.; Yamasaki, T.; Hatanaka, S.; Kojima, H.; Sakurai, T.; Takasu, Y.
Journal of Pharmacology and Experimental Therapeutics 257(1): 271-275
1991
ISSN/ISBN: 0022-3565 PMID: 1850466 Document Number: 376752
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.