Effect of the monoamine oxidase inhibitors clorgyline and pargyline on the hyperphagia of obese mice.

Obese-hyperglycemic mice (genotype ob/ob) have higher levels of hypothalamic norepinephrine than their normal-weight litter mates. Brain, as well as some other tissues, contains two types of monoamine oxidase (MAO). In this study we evaluated the effect of administering the Type A MAO inhibitor clorgyline (clorg) and the Type B MAO inhibitor pargyline (parg) on food intake. Acute administration of clorg/parg caused a temporary 50-90% decrease in food intake in normal mice, rats, golden, and Chinese hamsters, but did not alter the food intake of obese mice. To determine if alterations in the concentration of brain monoamines played a role in the effect of clorg/parg on food intake in mice, we determined the concentration of serotonin, dopamine, and norepinephrine in their cerebral cortex and hypothalamus after clorg/parg administration. When compared to normal mice, obese mice had a greater concentration of serotonin in their cerebral cortex and norepinephrine in their hypothalamus. As the obese mice had an equal or even greater increase in hypothalamic serotonin and norepinephrine concentration after clorg/parg administration than the normal mice, it is not likely that increased hypothalamic monoamines are responsible for the decreased food intake produced by clorg/parg administration. Obese and normal mice were treated with weekly injections of clorg/parg from 7 to 19 weeks of age. Clorg/parg produced a persistent 12% decrease in food intake and weight in obese, but not normal mice. Although the medication was discontinued at 19 weeks of age, the decrease in food intake and weight of the obese mice persisted until the time of sacrifice at 31-35 weeks. The combination of clorg/parg had a more profound effect on in vivo and in vitro MAO activity than equivalent amounts of the individual MAO inhibitors. Other anorectic agents such as D-amphetamine and fenfluramine had only a trivial in vitro effect on MAO activity.