Anticonvulsive effect of agmatine in mice.
The present study was designed to examine the effect of agmatine, the decarboxylated product of L-arginine by L-arginine decarboxylase, on convulsion in the mouse maximal electroshock (MES) test and mouse glutamate-induced convulsant test. MES convulsion and glutamate convulsion were respectively induced by an electrical stimulation (110 V, 0.3 s, 8 Hz) and by intracerebroventricular injection of glutamate (0.5 M, pH 7.4, 5microl). The results were expressed as the tonic and clonic time of convulsion in MES or percentage of mice with tonic hind-limb extension in glutamate-induced convulsant assay. Agmatine given intracerebroventricularly (2-16 mg/kg) or subcutaneously (10-160 mg/kg) significantly shortened the tonic and clonic times of convulsion in a dose-dependent manner in the mouse MES test. Glutamate (0.5 M, 5microl icv per mouse) induced an obvious convulsive response indicated by tonic hind-limb extension in mice, and agmatine (2-16 mg/kg icv) decreased the rate of mice with tonic hind-limb extension like NMDA receptor antagonist MK-801. The anticonvulsive effect of agmatine (80 mg/kg sc) on both the tonic and clonic times of convulsion lasted for more than 4 h after administration in the mouse MES test, which was twice that of barbital. Taken together, the results implicate that agmatine has obvious anticonvulsive effects, and its possible mechanism might be related to the antagonism of the function of NMDA receptors.
Su
Rui-Bin
RB
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, 100850, Beijing, PR China.
Wei
Xiao-Li
XL
Zheng
Jian-Quan
JQ
Liu
Yin
Y
Lu
Xin-Qiang
XQ
Li
Jin
J
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000376:Agmatine