Stereoselective Behavioral Effects of Cocaine and a Phenyltropane Analog

Intramuscular injections of the stereoisomers of cocaine and of its phenyltropane analog were compared for their effects on schedule-controlled behavior of squirrel monkeys. Monkeys responded by pressing a lever under a multiple schedule with alternating fixed-interval and fixed-ratio components; responding was maintained by presentation of food in some monkeys and by termination of a stimulus associated with electric shock in other monkeys. The levorotatory isomers, (-)-cocaine (0.09-2.7 mg/kg) and WIN 35,065-2 (0.006-0.2 mg/kg), had qualitatively similar effects which depended primarily on the type of component schedule (fixed-interval or fixed-ratio) that maintained responding. In the fixed-interval components, intermediate doses of each drug increased responding, whereas higher doses decreased responding. In the fixed-ratio components, each drug only decreased responding in a dose-related manner. The minimal effective dose of (-)-cocaine was about 10 times that of WIN 35,065-2. Although the dextrorotatory isomers, (+)-cocaine and WIN 35,065-3, also increased responding in the fixed-interval components and decreased responding in the fixed-ratio components in some monkeys, the doses required were 100 to 622 times the minimal effective doses of their enantiomers. The results show a high degree of stereoselectivity in the behavioral effects of both cocaine and its phenyltropane analog.