Tsuda M, Suzuki T, Misawa M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Addict Biol. 1997 Oct;2(4):455-60. doi: 10.1080/13556219772516.
The effect of the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC) on pentylenetetrazole (PTZ)induced diazepam-withdrawal seizure was examined in mice. The threshold for PTZ-induced seizure was markedly decreased by discontinuation of chronic diazepam treatment. The decrease in the seizure threshold of PTZ during diazepam withdrawal was significantly attenuated by pretreatment with alloTHDOC (10 and 20 mug/mouse, i.c.v.), which did not affect the seizure threshold of PTZ in chronically vehicle-treated mice. However, the loss of the righting reflex (LRR) induced by other GABAA receptor activators (pentobarbital and propofol) did not differ between control and diazepam-withdrawn mice. These findings provide the first demonstration that alloTHDOC may be able to suppress diazepam withdrawal signs, and that the sensitivity to the pharmacological effect of alloTHDOC via GABAA receptor may be enhanced in diazepam-with- drawn mice.
在小鼠中研究了神经甾体5α-孕烷-3α,21-二醇-20-酮（别孕烯醇酮，alloTHDOC）对戊四氮（PTZ）诱发的地西泮戒断性癫痫发作的影响。长期地西泮治疗停药后，PTZ诱发癫痫发作的阈值显著降低。别孕烯醇酮（10和20微克/小鼠，脑室内注射）预处理可显著减轻地西泮戒断期间PTZ癫痫发作阈值的降低，而别孕烯醇酮对长期给予溶媒的小鼠的PTZ癫痫发作阈值没有影响。然而，其他GABAA受体激动剂（戊巴比妥和丙泊酚）诱发的翻正反射消失（LRR）在对照组和地西泮戒断小鼠之间没有差异。这些发现首次证明别孕烯醇酮可能能够抑制地西泮戒断症状，并且在地西泮戒断小鼠中，通过GABAA受体对别孕烯醇酮药理作用的敏感性可能增强。
