CORRELATION BETWEEN CONVULSIVE ACTION AND METABOLISM OF ISONIAZID

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It is well known that the animal, after a large dose of isoniazid, has a short series of clonic movements followed by a tonic convulsion with a sustained contraction of all muscles. The seizures are characterized by a relatively prolonged interval of time between the administration of the drug and the onset of epileptiform seizures (1, 2). In our preceding paper (3), it has been described that this latent period differs with routes of administration and may be dependent on the isoniazid level in the central nervous system. Assuming that there existed a critical concentration in regard to the brain level of isoniazid, it would reasonably be considered that the convulsion does not appear until the brain level exceeds this critical point, even if an animal received isoniazid sufficient to cause a maximal seizure. Many reports, however, revealed that isoniazid undergoes a considerable metabolic change within a few hours after the administration to man and experimental animals (4, 5). Therefore, it is felt that an investigation of the distribution and metabolic pattern of isoniazid in the animals under the drug-induced seizures may serve to determine if any correlation existed between the convulsive action and the metabolism of this compound. The present paper describes distribution experiments in cats receiving a convulsive dose of isoniazid and also describes metabolic experiments carried out with mice receiving 14C-labelled isoniazid.
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CORRELATION BETWEEN CONVULSIVE ACTION AND METABOLISM OF ISONIAZID

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