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.
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.
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
T
T
Hashimoto
M
M
Kimori
Y
Y
Nakamura
K
K
Kuriyama
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D009419:Nerve Tissue Proteins; D010879:Piperazines; D014665:Vasodilator Agents; C050134:tamolarizine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase