NEUROPATHOLOGIC LESIONS IN DOGS AFTER PROLONGED ADMINISTRATION OF PHENYLISOPROPYLHYDRAZINE (JB 516) AND PHENYLISOBUTYLHYDRAZINE (JB 835)

¹ Laboratory of Experimental Pathology, National Institute of Arthritis and Metabolic Diseases, and Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Prolonged administration of the monoamine oxidase inhibitors, phenylisopropylhydrazine (JB 516) and phenylisobutyilhydrazine (JB 835), produced bilaterally symmetrical neuropathologic lesions involving the inferior olivary nucleus and, less frequently, the pyriform lobe, particularly the amygdaloid nuclei. In the inferior olivary nucleus, many neurons had a vacuolated cytoplasm. The lesions in the pyriform lobe had many microscopie features suggesting infarction. No such neuropathologic lesions were found in cats, rabbits, and squirrel monkeys given these two hydrazine inhibitors, and no such lesions were found in dogs following prolonged administrations of other monoamine oxidase inhibitors.

Proloisged administration of the two hydrazise inhsibitors caused in some dogs and other animnals testicular degenerations and huemolytic effects evidenced by a drop in hematocrit, an increase in hemosiderin deposition in the reticuloendothehial cells of the liver and spleen and occasionally by slightly increased cellularity of the bone marrow. These effects are considered to be nonspecific anti unrelated to the brain lesions.