1988 Fiscal Year Final Research Report Summary
Study on mechanism of convulsant activity of pyridon-carboxylic acid derivatives
| Project/Area Number |
62570302
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
SHIMADA Jingoro The Jikei University School of Medicine, 医学部, 助教授 (50056701)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Seiji The Jikei University School of Medicine (80165571)
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| Project Period (FY) |
1987 – 1988
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| Keywords | pyridon-carboxylic acid derivatives / non-steroidal anti-inflammatory drugs / convulsion / 痙攣 / GABA受容体 |
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| Research Abstract |
Since it was reported that new quinolones induced convulsions, we studied the effect of new quinolones on the receptor binding of gamma-aminobutyric acid (GABA),an inhibitory transmitter in the mammalian central nervous system, using mouse synaptic membranes. New quinolones inhibited GABA receptor binding in a concentration-dependent manner. The quinolone, which has unsubstituted piperzinyl group at carbon 7 had stronger inhibitory activity. The quinolone, which had N-methylated piperazinyl group, had weaker inhibitory activity. Scatchard analysis revealed that this inhibition of GABA receptor binding was due to the decrease of binding capacity and not to the change of the affinity of the receptor sites.
As it was reported that the patients treated with enoxacin and fenbufen, one of the non-steroidal anti-inflammatory drugs (NSAIDs), we studied the effect of new quinolones on GADA receptor bindings in the presnce of various NSAIDs. The inhibitory effect of new quinolones was enhanced in the presence of NSAIDs, except aspirin. Especially in the presence of biphenyl acetate, an active metabolite of fenbufen, the inhibitory activity of quinolones was remerkably enhanced. According to the Scatchard analysis, this inhibition of GABA receptor binding was due to the change of the receptor sites. And intraventricular injection of enoxacin in mouse brain did not induce convulsions(up to 10 nmol). However, when co-administered with biphenyl acetic acid (5 nmol), enoxacin(2.5 nmol) induced convulsions in all mice.
From these results, it was suggested that new quinolones might induce convulsions through the inhibition of GABA receptor binding. And it was also suggested that new quinolones might induce convulsions in their lower concentrations in the presence of NSAIDs.
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