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 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.
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Authors | T Nabeshima, Y Noda, K Tohyama, J Itoh, T Kameyama |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 178
Issue 2
Pg. 143-9
(Mar 20 1990)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 2328758
(Publication Type: Journal Article)
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Chemical References |
- Central Nervous System Agents
- Pyrrolidinones
- Picrotoxin
- nefiracetam
- Muscimol
- gamma-Aminobutyric Acid
- aniracetam
- Bicuculline
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Topics |
- Amnesia
(drug therapy, psychology)
- Animals
- Avoidance Learning
(drug effects)
- Bicuculline
(pharmacology)
- Central Nervous System Agents
(pharmacology)
- Male
- Mice
- Mice, Inbred Strains
- Muscimol
(pharmacology)
- Nervous System Diseases
(chemically induced, physiopathology)
- Picrotoxin
(pharmacology)
- Pyrrolidinones
(pharmacology)
- Synaptic Membranes
(drug effects)
- gamma-Aminobutyric Acid
(physiology)
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