Alley M C, Killam E K, Fisher G L
J Pharmacol Exp Ther. 1981 Apr;217(1):138-46.
Reports suggesting participation of trace metals in processes of seizure initiation and propagation in humans and experimental animals prompted an investigation of the relationship between copper and zinc status and seizure activity in the Senegalese baboon, Papio papio. An evaluation of serum trace metal concentrations in three species of nonhuman primates revealed the presence of elevated zinc levels in P. papio moderately sensitive to photically induced seizures, compared with mildly seizure-prone and nonseizure-prone P. papio as well as nonseizure-prone primates. Papio cynocephalus and Macaca mulatta. By contrast, copper levels appeared similar in all three species. Chronic oral treatment with D-penicillamine, a chelating agent, resulted in marked protection against photic-induced seizures in the P. papio baboon, as well as changes in the trade metal status of serum and urine. Oral dosages of 30 to 40 mg/kg/day were sufficient to establish anticonvulsant effect over a period of 4 to 9 weeks in all animals tested without signs of toxicity or tolerance. Results suggest that metal chelation treatment may represent a new approach to the management of certain forms of human epilepsy.
有报告表明痕量金属参与人类和实验动物癫痫发作的起始和传播过程，这促使人们对塞内加尔狒狒（Papio papio）体内铜和锌状态与癫痫活动之间的关系展开研究。对三种非人灵长类动物血清痕量金属浓度的评估显示，与轻度易患癫痫和不易患癫痫的狒狒以及不易患癫痫的灵长类动物（豚尾狒狒和恒河猴）相比，对光诱导癫痫发作中度敏感的狒狒体内锌水平升高。相比之下，所有三个物种的铜水平似乎相似。用螯合剂D-青霉胺进行慢性口服治疗，可显著保护狒狒免受光诱导癫痫发作，并导致血清和尿液中痕量金属状态发生变化。在所有受试动物中，30至40毫克/千克/天的口服剂量足以在4至9周内产生抗惊厥作用，且无毒性或耐受性迹象。结果表明，金属螯合治疗可能是治疗某些类型人类癫痫的一种新方法。
