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


CONCLUSIONS
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.
Chen
Zhong
Z
Department of Pharmacology; Department of Psychology, School of Medicine, Zhejiang University, Hangzhou 310031, China. chenzfl@hotmail.com
Li
Wei-Dong
WD
Zhu
Li-Jun
LJ
Shen
Ying-Jie
YJ
Wei
Er-Qing
EQ
D000818:Animals; D004357:Drug Synergism; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology*; D007696:Kindling, Neurologic; D008297:Male; D010433:Pentylenetetrazole; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D006639:Histidine; D006632:Histamine; D011738:Pyrilamine; C052075:thioperamide; D010433:Pentylenetetrazole