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ANTICONVULSANT EFFECT OF A NOVEL TRH ANALOG (DN-1417) ON AMYGDALOID KINDLED SEIZURE Kiyoshi Morimoto 1 , Takashi Moriwake 1 , Takako Akiyama 1 , Mitsumoto Sato 1 , Saburo Otsuki 1 1Department of Neuropsychiatry, Okayama University Medical School pp.189-195
Published Date 1983/2/1
DOI https://doi.org/10.11477/mf.1406205077
  • Abstract
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Anticonvulsant effects of DN-1417, a novel TRH analog, were examined in kindling prepara-tions which had been established as an experi-mental model of epilepsy (secondary generalized seizure).

Eleven amygdaloid kindled cats were tested. After intravenous administration of DN-1417, final electroconvulsive threshold (FET) stimulation was given to the amygdala. Dose of DN-1417 (0. 5, 1, 2 or 4 mg/kg) and FET stimulation time (5, 10, 15, 20 or 30 min. after the administration) were flexible in this study. Firstly, changes in autonomic nervous manifestations and general behavior were observed. Secondly, acute anticon-vulsant effects of DN-1417 on both behavioral seizure and afterdischarge induced by amygdaloid stimulation were examined. Further more, changes in FET was examined at 24 hours after the drug administration.

The following results were obtained :

1) Autonomic nervous manifestations including vomiting, evacuating of the bowels, hypersaliva-tion and hyperpnea appeared in 7 out of 11 cats, while stereotyped behavior appeared in only one cat.

2) DN-1417 suppressed the kindled generalized seizure in 10 out of 11 cats. Generalized seizure was either changed into partial seizure or blocked completely. But acute anticonvulsant effect of DN-1417 lasted for very short time (5~20 min.), and effective doses ranged from 1 to 4 mg/kg without dose-related efficacy. These characteristics of anticonvulsant effect are identical to these of indirect dopamine agonist, i. e. methamphetamine, nomifensine and cocaine. The acute anticonvulsant effects of DN-1417 differed from those of such representative antiepileptics as Phenytonin, Phe-nobarbital and Carbamazepine, which have dose-related and lasted efficacy on the amygdaloid kindled seizure. An assumption that dopamine may relate to the anticonvulsant effect of DN-1417 was made.

3) Following the positive anticonvulsant effect, FET was elevated after 24 hours of the drug administration in 4 out of 10 cats. This effect could be reconfirmed and persisted for 9 to 40 days. Such long-lasting anticonvulsant effect has never reported in terms of kindling preparations. Further study is proceeded for an exploration of the mechanism of the long-lasting effect.


Copyright © 1983, Igaku-Shoin Ltd. All rights reserved.

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電子版ISSN 2185-405X 印刷版ISSN 0006-8969 医学書院

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