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Acta Pharmacol Sin. 2002 Apr;23(4):361-6.

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

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Department of Pharmacology; Department of Psychology, School of Medicine, Zhejiang University, Hangzhou 310031, China.



The effect of histidine on pentylenetetrazole-induced seizures was investigated in rats.


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.


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.


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.

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