Experimental study of the effects of imidazol, papaverine and histamine on convulsive-seizure reactivity.

In experiments on male albino rats and mice a study is made of the effects of imidazol which is a phosphodiesterase stimulator, papaverine which inhibits phosphodiesterase and histamine which stimulates adenylate cyclase, on the convulsive-seizure reactivity. The substances are introduced intraventricularly and intracerebroventricularly, imidazol also intraperitoneally in different doses and at different intervals before the convulsive agent. Electrical, pentylenetetrazol (Cor) and strychnine convulsion models are used. The effect of imidazol on the spontaneous cortical bioelectrical activity is studied throuth its i. v. administration in rabbits. Imidazol markedly increases the convulsive reactivity, and in large doses it alone results in electrographic and motor convulsions. Paperine slightly lowers the convulsive-seizure reactivity only in pentylenetetrazol convulsions. The results obtained and their comparison with the results of previous experiments of ours with other drugs affecting the cyclic adenosinemonophosphate (cAMP) system, such as lithium, haloperidol, caffeine and theophyline, do not permit to assume a considerable significance of the influence of these substances (in the doses tested) on the cAMP system in the mechanisms of their effects on the convulsive-seizure reactivity.

On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive-seizure reaction.

In experiments on male albino mice it has been established that upon intracerebroventricular administration in doses of 50, 100 and 300 mug per mouse GABA markedly inhibits the convulsive-seizure reactions in pentylenetetrazol and electroconvulsions and has no substantial effect on strychnine convulsions (the dose of 300 mug is toxic). Diethyldithiocarbamate (DDC) in a dose of 400 mg/kg, introduced i.p. 3 hours in advance, increases the convulsive reactivity in pentylenetetrazol and electroconvulsions. On the background of DDC the inhibitory effect of GABA is expressed only in antagonizing of the DDC effect increasing the convulsive reactivity. Alpha-methyl-paratyrosine (a-MT) in a dose of 250 mg/kg, introduced i.p. 4 hours in advance, has no substantial effect on the convulsive reactivity. On the background of alpha-MT the inhibitory effect of GABA in electroconvulsions does not change essentially, however, in pentylenetetrazol convulsions the GABA effect is practically not manifested. The results obtained show that the changes in the correlations between the catecholamines and GABA in the central nervous system result in substantial changes in the convulsive-seizure reactivity. The lower catecholamines level does not permit the marked manifestation of the GABA inhibitory effect. However, GABA counteracts to a certain extent the rise in the convulsive reactivity as a result of the drop in the brain level of the catecholamines.