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Neurologic, neuropathologic, and neurochemical effects of prolonged administration of phenylisopropylhydrazine , phenylisobutylhydrazine , and other monoamine oxidase inhibitors

, : Neurologic, neuropathologic, and neurochemical effects of prolonged administration of phenylisopropylhydrazine , phenylisobutylhydrazine , and other monoamine oxidase inhibitors. Jour Pharmacol And Exptl Therap 137(3): 334-343

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. The one sign most consistently associated with a lesion in the inferior olivary nucleus was nystagmus. Pyri-doxine 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 hystagmus 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.


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