Abstract

Thirty-six hydrazides have been tested for their characteristic effect, i.e., the production of repeated maximal seizures. The most potent compound in this series is thiocarbohydrazide which, on a molar basis, is 27 times more active than isoniazid and 4 times more active than thiosemicarbazide. Effective anticonvulsants against hydrazide seizures are in descending order of potency: phenobarbital, phenacemide, atrolactamide, trimethadione, mesantoin and sodium bromide. Diphenyihydantoin modifies the seizure pattern but does not protect against convulsions or death. Neither the liberation of ammonia nor the potentiation of histamine appear to be factors in the hydrazide seizures. While large doses of acetone prevent the seizures, paradoxically acetone semicarbazone is twice as potent as a convulsant than is semicarbazide. The convulsant activity of the most active compounds can not be correlated with their ionization constants. Because of the long latent period before the onset of convulsions, it is postulated that hydrazides produce seizures by a biochemical action which is not specifically corrected by any of the antidotes reported in this study.