Stone W E, Javid M J
Arch Int Pharmacodyn Ther. 1979 Jul;240(1):66-78.
Anticonvulsants were tested on mice for their effectiveness against different chemical convulsants. Ethosuximide is very effective against pentylenetetrazol (PTZ), but ineffective against 3-mercaptopropionate (3-MP) which is an inhibitor of gamma-aminobutyrate (GABA) synthesis. Trimethadione, chlordiazepoxide and mesuximide are less effective against 3-MP than against PTZ. The same tendency was apparent, though falling short of statistical significance, with phenobarbital, mephenytoin, carbamazepine and valproic acid, whereas aminooxyacetic acid (AOAA) appeared to be somewhat more effective against 3-MP than against PTZ. Several anticonvulsants were tested also against bicuculline (BIC), picrotoxin (PIC) and bemegride (BEM), and profiles depicting their relative capacities to antagonize the convulsants were constructed. These show major differences and few resemblances. Likewise the convulsants show little resemblance to each other in their patterns of sensitivity to different anticonvulsants. The data do not support the concept that PTZ, BEM, BIC or PIC induce seizures primarily by blockading GABA-mediated inhibition, since their patterns are so unlike that of 3-MP. The profiles of clinically used anticonvulsants suggest that none of those tested acts primarily on the GABA system, since all are so unlike that of AOAA.
在小鼠身上测试了抗惊厥药对不同化学惊厥剂的有效性。乙琥胺对戊四氮（PTZ）非常有效，但对作为γ-氨基丁酸（GABA）合成抑制剂的3-巯基丙酸（3-MP）无效。三甲双酮、氯氮卓和甲琥胺对3-MP的效果比对PTZ的效果差。苯巴比妥、美芬妥因、卡马西平和丙戊酸也有同样的趋势，尽管未达到统计学显著性，而氨氧乙酸（AOAA）对3-MP的效果似乎比对PTZ的效果稍好。还测试了几种抗惊厥药对荷包牡丹碱（BIC）、印防己毒素（PIC）和贝美格（BEM）的作用，并构建了描述它们拮抗惊厥剂相对能力的图谱。这些图谱显示出主要差异，相似之处很少。同样，惊厥剂对不同抗惊厥药的敏感性模式彼此之间也很少相似。数据不支持PTZ、BEM、BIC或PIC主要通过阻断GABA介导的抑制作用来诱发癫痫发作的概念，因为它们的模式与3-MP的模式非常不同。临床使用的抗惊厥药的图谱表明，所测试的药物中没有一种主要作用于GABA系统，因为它们都与AOAA的图谱非常不同。
