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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)271-275
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume257
Issue number1
Publication statusPublished - 01-01-1991
Externally publishedYes

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Amnesia
Muscarinic Receptors
GABA-A Receptors
Cycloheximide
gamma-Aminobutyric Acid
aniracetam
Cholinergic Receptors
GABA Antagonists
Picrotoxin
Scopolamine Hydrobromide
Bicuculline
Animal Models
Binding Sites
nefiracetam
Brain
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Nabeshima, Toshitaka ; Tohyama, K. ; Murase, K. ; Ishihara, S. ; Kameyama, T. ; Yamasaki, T. ; Hatanaka, S. ; Kojima, H. ; Sakurai, T. ; Takasu, Y. ; Shiotani, T. / Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABA(A) and muscarinic receptors induced by cycloheximide. In: Journal of Pharmacology and Experimental Therapeutics. 1991 ; Vol. 257, No. 1. pp. 271-275.
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author = "Toshitaka Nabeshima and K. Tohyama and K. Murase and S. Ishihara and T. Kameyama and T. Yamasaki and S. Hatanaka and H. Kojima and T. Sakurai and Y. Takasu and T. Shiotani",
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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, vol. 257, no. 1, pp. 271-275.

Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABA(A) and muscarinic receptors induced by cycloheximide. / Nabeshima, Toshitaka; Tohyama, K.; Murase, K.; Ishihara, S.; Kameyama, T.; Yamasaki, T.; Hatanaka, S.; Kojima, H.; Sakurai, T.; Takasu, Y.; Shiotani, T.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 257, No. 1, 01.01.1991, p. 271-275.

Research output: Contribution to journalArticle

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T1 - Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABA(A) and muscarinic receptors induced by cycloheximide

AU - Nabeshima, Toshitaka

AU - Tohyama, K.

AU - Murase, K.

AU - Ishihara, S.

AU - Kameyama, T.

AU - Yamasaki, T.

AU - Hatanaka, S.

AU - Kojima, H.

AU - Sakurai, T.

AU - Takasu, Y.

AU - Shiotani, T.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - 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.

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