Effects of histidine, a precursor of histamine, on pentylenetetrazole-induced seizures in rats.

作者：Zhong Chen, Weidong Li, Li‐Jun Zhu, Yingjie Shen, Er-Qing Wei · 发表于：PubMed · 年份：2002 · 被引用次数：57 · 研究领域：Mast cells and histamine、Polyamine Metabolism and Applications、Sleep and Wakefulness Research

AIM: The effect of histidine on pentylenetetrazole-induced seizures was investigated in rats. METHODS: Chemical kindling was elicited by repeated ip injection a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every 48 h until the occurrence of seizure stages 4-5, and seizure activity of kindling was recorded for 30 min. RESULTS: In the kindling development process, ip injection of histidine (200, 500 mg/kg), a precursor of histamine, prolonged latency for the onset of myoclonic jerks and the clonic generalized seizure, and inhibited seizure stage in a dose-dependent manner. In the kindling challenge process, histidine (500, 1000 mg/kg) and H3 antagonist thioperamide (10, 20 microg) al so showed a significant anticonvulsant effect. The inhibitory action of histidine was enhanced significantly by thioperamide (5 microg), however, was antagonized by both alpha fluoromethylhistidine (20 microg), a selective histidine decarboxylase inhibitor and H1 ant agonist pyrilamine (2, 5 mg/kg), dose-dependently and significantly. In addition, H2 antagonist zolantidine appeared no appreciable effect, even at a dose of 10 mg/kg. CONCLUSION: These results indicated that brain endogenous histamine may play certain important role in protect against generalized clonic seizures, its action may via presynaptic H3-receptors and postsynaptic H1-receptors.