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Brain and Nerve No to Shinkei Volume 35, Issue 5 （May 1983）

Brain and Nerve 脳と神経 35巻5号（1983年5月発行）

Japanese English

原著

TRH analog （DN−1417）の抗けいれん効果　第II報，TRH・Tとの比較—キンドリングモデルを用いた研究 ANTICONVULSANT EFFECT OF A NOVEL TRH ANALOG (DN-1417) ON AMYGDALOID KINDLED SEIZURE II:COMPARISON WITH TRH TYTRATE 森本清 ¹ , 森分隆 ¹ , 佐藤光源 ¹ , 大月三郎 ¹ Kiyoshi Morimoto ¹ , Takashi Moriwake ¹ , Mitsumoto Sato ¹ , Saburo Otsuki ¹ ¹岡山大学医学部神経精神医学教室 ¹Department of Neuropsychiatry, Okayama University Medical School pp.501-504

発行日 1983年5月1日 Published Date 1983/5/1

DOI https://doi.org/10.11477/mf.1406205125

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Abstract 文献概要
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　抄録　TRH analogのひとつであるDN−1417は，最近注目されているneuropeptideのひとつであり，難治性てんかんに対し有効例の報告もある。前報で私どもは，二次全汎化モデルとして確立されているキンドリングモデルを用いたDN−1417の抗けいれん効果の評価実験結果を報告した。今回は，6匹の扁桃核キンドリングネコを用い，DN−1417の場合と同様の実験方法でTRH・Tの抗けいれん効果に関する研究をおこなった。その結果，TRH・Tにも有効時間の短い，用量依存性を欠く急性抗けいれん効果と，少数例ではあるが長期間持続性の電気けいれん閾値上昇効果とがあり，DN−1417とほぼ同一の抗けいれん効果のあることが判明した。このことより，TRHの一般薬理作用として，抗けいれん効果のあることを指摘し，さらに，DN−1417の抗けいれん効果にはDA系よりもNA系の関与が大きいことを考察した。

We reported previously that a novel TRH analog, DN-1417 had anticonvulsant effects in kindling cat preparations which had been estab-lished as an experimental model of epilepsy. For the purpose of comparison with the anticonvulsant effect of DN-1417, the effect of TRH Tytrate (TRH?T) was examined in 6 amygdaloid kindled cats.

After intravenous administration of TRH?T, final electroconvulsive threshold (FET) stimulation was given to the amygdala. Dose of TRH?T (O. 5, 1, 2 or 4 mg/kg) and FET stimulation time (5, 10, 15, or 20 min. after the administration) were flexible in this study. Firstly, changes in autono-mic manifestations and in awake resting EEG induced by TRH?T administration were investiga-ted in kindled cats. Secondly, acute anticonvulsant effects of TRH?T on both behavioral seizure and afterdischarge induced by amygdaloid stimulation were examined. Furthermore, changes in FET were examined 24 hours after the drug administra-tion.

The following results were obtained:

1) Autonomic manifestations including hypersa-livation and hyperpnea were more prominent after TRH?T administration than those when the same dosage of DN-1417 was used. There was no change on awake resting EEG of kindled cats, in which the frequency of interictal discharge was unchanged following either TRH?T or DN-1417.

2) TRH?T suppressed the kindled generalized seizure in 4 out of 6 cats (cf. DN-1417 ; 10 out of 11). Such acute anticonvulsant effect of TRH?T lasted for several minutes without dose-dependent response. These characteristic anticonvulsant effects of TRH?T were identical to those of DN-1417 as reported previously. Since TRH?T and DN-1417 have common pharmacological action on brain noradrenergic system, it is suggested that central noradrenergic system may participate in the acute anticonvulsant effect of DN-1417.

3) FET was elavated after 24 hours of TRH?T administration in 3 out of 6 cats (cf. DN-1417 ; 4 out of 11) in which acute anticonvulsant effect was positive. This effect was duplicated and persisted for 4 to 60 days. Such long-lasting anticonvulsant effect of TRH?T has never been reported using kindling preparations.