[The intracerebral route of kynurenine administration is one of the reasons for the resistance of kynurenine-induced seizures to diazepam].
It has been shown many times that in experiments on mice systemic administration of anticonvulsive doses of diazepam caused a 15-20-fold higher effect against the endogenous convulsant kynurenine (injection into the brain ventricles) than against corasol (systemic injection). In the present work diazepam (0.5-2.0 mg/kg, intraperitoneal injection) prevented convulsions induced in nonbred and C57B1/6 mice by equally effective doses of corasol injected subcutaneously (80 mg/kg) better than in injection into the brain ventricles (500 micrograms). In injection of the three drugs into the ventricles diazepam (0.5-10 micrograms) relieved to a similar degree convulsions induced by equally effective doses of corasol (500 micrograms) and kynurenine (50 micrograms). It follows from this that the unique resistance the kynurenine convulsions to diazepam is due to the fact that only kynurenine is injected into the brain ventricles whereas all the other convulsants compared with it are administered systemically. It is suggested that besides the route of administration, the more significant dependence of kynurenine convulsions on GAMA(B) receptors and the activity of the brain dopaminergic system is responsible for the difference in the diazepam sensitivity of kynurenine and corasol convulsions.
Laboratory of Psychopharmacology, Bechterev Research Psychoneurological Institute, St. Petersburg, Russia.
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Lapin
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D016009:Chi-Square Distribution; D003292:Convulsants / Q000008:administration & dosage*; D003975:Diazepam / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007737:Kynurenine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010433:Pentylenetetrazole / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*; D013331:Strychnine / Q000008:administration & dosage
D000927:Anticonvulsants; D003292:Convulsants; D007737:Kynurenine; D013331:Strychnine; D003975:Diazepam; D010433:Pentylenetetrazole