Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions

Toshitaka Nabeshima, Noda Yukihiro Noda, Tohyama Keiko Tohyama, Itoh Jiroh Itoh, Kameyama Tsutomu Kameyama

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 and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam amelioratedbicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 ± 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (- log IC50 = 3.63 M; Hill value = 0.37 ± 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.

Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalEuropean Journal of Pharmacology
Volume178
Issue number2
DOIs
Publication statusPublished - 20-03-1990
Externally publishedYes

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aniracetam
Amnesia
Picrotoxin
Muscimol
GABA-A Receptors
Inhibitory Concentration 50
GABA Antagonists
gamma-Aminobutyric Acid
Animal Models
nefiracetam

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nabeshima, Toshitaka ; Yukihiro Noda, Noda ; Keiko Tohyama, Tohyama ; Jiroh Itoh, Itoh ; Tsutomu Kameyama, Kameyama. / Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. In: European Journal of Pharmacology. 1990 ; Vol. 178, No. 2. pp. 143-149.
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Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. / Nabeshima, Toshitaka; Yukihiro Noda, Noda; Keiko Tohyama, Tohyama; Jiroh Itoh, Itoh; Tsutomu Kameyama, Kameyama.

In: European Journal of Pharmacology, Vol. 178, No. 2, 20.03.1990, p. 143-149.

Research output: Contribution to journalArticle

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