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