Marangos P J, Martino A M, Paul S M, Skolnick P
Psychopharmacology (Berl). 1981;72(3):269-73. doi: 10.1007/BF00431829.
The induction of generalized tonic-clinic seizures in mice by the methylxanthine stimulant caffeine is described. These seizures are indistinguishable in quality from those induced by pentylenetetrazol (PTZ), and pretreatment with low doses of caffeine potentiates PTZ-induced seizures. Benzodiazepines inhibit caffeine-induced seizures with a rank order potency that parallels their affinities for the central nervous system (CNS) benzodiazepine receptor in vitro. Inosine, a purine that has recently been shown to be a competitive inhibitor of [3H] diazepam binding in vitro, antagonizes caffeine-induced seizures, while 7-methyl-inosine, a purine that lacks receptor binding inhibitory activity, has no effect on seizures. Since the benzodiazepines, inosine, caffeine, and pentylenetetrazol all competitively inhibit [3H] diazepam binding and have marked effects on inducing or antagonizing seizures, further study of this receptor-ligand system may provide additional insights that concern possible biochemical mechanisms of seizures.
本文描述了甲基黄嘌呤兴奋剂咖啡因在小鼠中诱发全身性强直阵挛性癫痫发作的情况。这些癫痫发作在性质上与戊四氮（PTZ）诱发的发作并无区别，且低剂量咖啡因预处理可增强PTZ诱发的癫痫发作。苯二氮䓬类药物抑制咖啡因诱发的癫痫发作的效力顺序与其在体外对中枢神经系统（CNS）苯二氮䓬受体的亲和力平行。肌苷是一种嘌呤，最近已被证明在体外是[3H]地西泮结合的竞争性抑制剂，它可拮抗咖啡因诱发的癫痫发作，而7-甲基肌苷是一种缺乏受体结合抑制活性的嘌呤，对癫痫发作无影响。由于苯二氮䓬类药物、肌苷、咖啡因和戊四氮均能竞争性抑制[3H]地西泮结合，且对诱发或拮抗癫痫发作有显著影响，因此对该受体-配体系统的进一步研究可能会为癫痫发作的可能生化机制提供更多见解。
