Abstract

Prolonged administration in dogs of phenylisopropylhydrazine (JB 516) or phenylisobutylhydrazine (JB 835) consistently produced marked neurologic effects, including ataxia, tremors, nystagmus, and impaired motor coordination. After prolonged administration of either JB 516 or JB 835, most dogs developed neurologic lesions, usually in the inferior olivary nucleus, or in the pyriform lobe, or both. These lesions are described in the accompanying paper by Highman and Maling (1962). The one sign most consistently associated with a lesion in the inferior olivary nucleus was nystagmus. Pyridoxine did not prevent the neurologic signs or lesions. Such lesions were not found in cats, rabbits, and squirrel monkeys given JB 516, or in dogs given other inhibitors. Cats and squirrel monkeys showed an impaired motor coordination after prolonged treatment with JB 516, but nystagmus was not seen in these species. Dogs showed markedly elevated serotonin and unchanged norepinephrine levels in brain stem and spinal cord after prolonged administration of all potent monoamine oxidase inhibitors. These findings demonstrate the danger of delayed toxicity with chronic administration of some drugs.