TRH analog （DN−1417）の発作後抑制期に与える影響—キンドリングモデルを用いた研究

THE EFFECT OF A NOVEL TRH ANALOG (DN-1417) ON POSTICTAL SEIZURE INHIBITION IN AMYGDALOID KINDLED CATS

　抄録　TRHの誘導体のひとっであるDN−1417は動物実験ならびに臨床治験で抗けいれん効果が注目されている。今回は，キンドリングネコに11時間間隔で反復電気刺激を加えることにより得られる発作後抑制期（postictal seizure inhibition，以下PSI）に及ぼすDN−1417の効果を検討した。対象は6匹の両側扁桃核キンドリングネコで，PSIは3時聞から6時間の範囲であった（control session）。これに対し，　DN—1474 4mg／kgの静脈内投与20分後からPSIを測定すると全例について延長が認められ，抑制期は5時間から8時間以上に及んでいた（drug session）。また両　sessionの初回刺激の際の脳波記録では，後発射の終焉に連続してみられる発作後の平坦脳波期の短縮が観察された。これとは別に2匹のネコについてTRH・tartrate （TRH・T）4mg／kgを投与後，同様の実験を行った場合にもPSIの延長が観察された。このことは，外来性のTRH誘導体もしくはTRH・Tが生体に存在する長期持続性の発作抑制機序に影響を与えることを示しており，その際の脳内生化学的機序に対し若干の考察をした。

Anticonvulsant and prophylactic effects of DN-1417, a novel TRH analog, were reported previ-ously in kindled cat preparations which had been established as an experimental model of epilepsy. This study was conducted to examine an effect of DN-1417 on postictal events including postictal seizure inhibition (PSI).

A recycling paradigm consisted of 8 amygdaloid stimuli at 1 hour intervals was applied to evaluate the PSI. Six of bilateral amygdaloid kindled cats were used. In control session, the left amygdala had been stimulated at final electroconvulsive threshold at 1 hour intervals in all cats. In drug session, the cats were pretreated with DN-1417 (4 mg/kg, i. v.) and exposed to recycling paradigm 20 minutes after the administration. The interval of each session was at least 2 weeks EEG record-ings and behavioral observations were carried out at the same time. Effects of TRH tartrate (4 mg/ kg, i. v.) on PSI was also investigated in 2 cats at the same paradigm.

PSI was significantly prolonged and postictal EEG silence was significantly shortened by DN-1417. The pretreatment of TRH tartrate showed an prologation of PSI in 2 cats respectively.

These results suggest that administrated TRH analog or TRH may inhibit an occurence of sub-sequent seizures and prevent the epileptic status.