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Pharmacological analysis of a new anorexic substance: 5-hydroxy-5(4'-chlorophenyl)-2, 3-dihydro-5H-imidazo-(2, 1-a) isoindole (Mazindol).

5-Hydroxy-5-(4'-chlorophenyl-2, 3-dihydro-5H-imidazo (2, 1-a)isoindole (mazindol), a novel tricyclic compound, has been shown to suppress food consumption in rats at doses causing weak central stimulation and little effects on blood pressure or heart rate. The substance produces dose-related decreases in the consumption of orange juice in cebus monkeys trained on an operant behavior schedule. The compound did not alter cardiac or pulmonary hemodynamics in the anesthetized dog but provided potentiation of norepinephrine pressor responses. Mazindol also demonstrated potent but incomplete antagonism of reserpine-induced hypothermia in mice, antagonism of tetrabenazine catalepsy in rats, and suppression of mouse-killing behavior of rats. Suppression of mouse-killing was reduced by lesions placed in the septal area of the brain. Brain monoamine oxidase or catechol-o-methyl-transferase activities were not altered, although preliminary experiments showed that mazindol reduced uptake of norepinephrine in brain tissue.