Grant K A, Hellevuo K, Tabakoff B
Division of Clinical and Biologic Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD.
Alcohol Clin Exp Res. 1994 Apr;18(2):410-4. doi: 10.1111/j.1530-0277.1994.tb00034.x.
Ethanol-dependent mice were treated with the 5-HT3 antagonist MDL 72222 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10, and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose-dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after withdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display any seizures. Treatment with another 5-HT3 antagonist, ICS 205-930 (23 and 46 mg/kg), or the 5-HT2 receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure.
对乙醇依赖型小鼠在戒断乙醇后给予5-羟色胺3（5-HT3）拮抗剂MDL 72222进行治疗。在戒断后0、4和7小时，给予单位剂量（0、5.6、10和17.0毫克/千克）的MDL 72222进行治疗，剂量依赖性地加重了乙醇戒断性癫痫发作的严重程度。在戒断后5小时给予单剂量（17毫克/千克）的MDL 72222进行治疗，也加重了乙醇戒断性癫痫发作的严重程度。用MDL 72222（56毫克/千克）治疗未接触过乙醇的小鼠未出现任何癫痫发作。用另一种5-HT3拮抗剂ICS 205-930（23和46毫克/千克）或5-HT2受体拮抗剂酮色林进行治疗，对乙醇戒断性癫痫发作没有影响。这些发现表明，MDL 72222选择性地增强了慢性乙醇暴露后对戒断性癫痫发作的敏感性。
