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

Article date: 1990/3/20

PubMed ID: 2328758

Journal name: European journal of pharmacology (ISSN: 0014-2999)


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 ameliorated bicuculline-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.

This document is available from: http://directlinks.cc/files/muscimol/2328758.pdf

Author List: Nabeshima T, Noda Y, Tohyama K, Itoh J, Kameyama T

Publication Types: Journal Article

Substances mentioned in the article: Central Nervous System Agents; Pyrrolidinones; Picrotoxin; nefiracetam; Muscimol; gamma-Aminobutyric Acid; aniracetam; Bicuculline;

Mesh terms: Amnesia/drug therapy; Animals; Avoidance Learning/drug effects; Bicuculline/pharmacology; Central Nervous System Agents/pharmacology; Male; Mice; Mice, Inbred Strains; Muscimol/pharmacology; Nervous System Diseases/chemically induced; Picrotoxin/pharmacology; Pyrrolidinones/pharmacology; Synaptic Membranes/drug effects; gamma-Aminobutyric Acid/physiology;

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