EFFECTS OF COCAINE ALONE AND IN COMBINATION WITH MAZINDOL IN HUMAN COCAINE ABUSERS

Mazindol is a catecholamine reuptake inhibitor that blocks binding of cocaine at the dopamine reuptake site. This study was conducted to det ermine whether the acute administration of mazindol modulates the phar macological effects of intravenous cocaine in humans. In a crossover s tudy, twelve acute drug conditions were tested in randomized order und er double-blind, double-dummy conditions in eight cocaine abusers. Coc aine (0, 12.5, 25 and 50 mg, i.v.) was administered in combination wit h mazindol (0, 1 and 2 mg given orally 2 hr before the cocaine injecti on). Physiological and subject- and observer-rated responses were meas ured. Cocaine and mazindol alone both significantly increased heart ra te and blood pressure. Cocaine increased ratings on stimulant-like sub jective effect measures, including desire for cocaine; mazindol had mi ld, stimulant-like subjective effects. There were significant interact ions between the effects of cocaine and mazindol on heart rate and blo od pressure, with combinations producing significantly larger and more sustained increases compared with cocaine alone. There was no evidenc e that mazindol substantially altered the magnitude or profile of the subjective effects of cocaine, including cocaine-induced craving for c ocaine. These results do not support the utility of acute administrati on of mazindol in the treatment of cocaine abusers through a mechanism of modulation of cocaine's subjective effects. Furthermore, mazindol treatment may increase the cardiovascular risks of cocaine.