Effect of NC-1100 [1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride] on gamma-aminobutyric acid (GABA) metabolism in rat brain: analysis using stroke-prone spontaneously hypertensive rat.

Article date: 1989/6/1

PubMed ID: 2770051

Journal name: Japanese journal of pharmacology (ISSN: 0021-5198)


Effects of oral administration of NC-1100 on the metabolism of neuroactive amino acids in rat brain were studied using stroke-prone spontaneously hypertensive (SHR-SP) and Wistar Kyoto rats. The repeated administration of NC-1100 induced a significant increase of gamma-aminobutyric acid (GABA) content in the cerebellum and medulla oblongata of SHR-SP. The decrease of aspartic acid contents in the cerebellum and medulla oblongata of SHR-SP was also noted following NC-1100 administration. Although the activity of L-glutamic acid decarboxylase did not change in these cerebral areas, the activity of GABA-transaminase:succinic semialdehyde dehydrogenase was found to be significantly reduced in the cerebellum of SHR-SP following the repeated administration of NC-1100. The turnover rate of GABA was also significantly reduced in the cerebellum and medulla oblongata of SHR-SP. It was also found that the spontaneous release of preloaded [3H]GABA from cerebral cortical slices was significantly retarded by the continuous oral administration of NC-1100. These results suggest that NC-1100 may be a drug inducing the increase of GABA in the cerebellum and medulla oblongata following continuous administration, especially in animals having hypertension associated cerebrovascular disorders such as SHR-SP.

This document is available from: http://directlinks.cc/files/muscimol/2770051.pdf

Author List: Hashimoto T, Kimori M, Nakamura Y, Kuriyama K

Publication Types: Journal Article

Substances mentioned in the article: Amino Acids; Nerve Tissue Proteins; Piperazines; Vasodilator Agents; tamolarizine; Muscimol; gamma-Aminobutyric Acid; 4-Aminobutyrate Transaminase; Glutamate Decarboxylase;

Mesh terms: 4-Aminobutyrate Transaminase/metabolism; Amino Acids/metabolism; Animals; Brain/drug effects; Cerebrovascular Disorders/metabolism; Glutamate Decarboxylase/metabolism; In Vitro Techniques; Male; Muscimol/metabolism; Nerve Tissue Proteins/metabolism; Piperazines/pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Synapses/drug effects; Vasodilator Agents/pharmacology; gamma-Aminobutyric Acid/metabolism;

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