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

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

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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 GABA(A) 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 GABAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.

元の言語English
ページ(範囲)271-275
ページ数5
ジャーナルJournal of Pharmacology and Experimental Therapeutics
257
発行部数1
出版物ステータスPublished - 1991

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Nabeshima, T., Tohyama, K., Murase, K., Ishihara, S., Kameyama, T., Yamasaki, T., Hatanaka, S., Kojima, H., Sakurai, T., Takasu, Y., & Shiotani, T. (1991). Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABA(A) and muscarinic receptors induced by cycloheximide. Journal of Pharmacology and Experimental Therapeutics, 257(1), 271-275.