Stereoselective effects of cocaine

The stereoselectivity of several effects of cocaine was examined. Traditional behavioral effects of psychomotor stimulants, including increases in locomotor behavior in mice, increases in rates of operant behavior maintained under fixed-interval schedules in monkeys, and discriminative stimulus effects in rats were assessed. Toxic effects, including convulsions and lethality, were assessed in mice. The (-)-enantiomer of cocaine produced increases in locomotor activity at doses at least 340-fold lower than the highest doses of the (+)-enantiomer that were inactive. Increases in operant behavior were also obtained at doses of the (-)-enantiomer that were at least 340-fold lower than the highest doses of the (+)-enantiomer that were inactive. The ED(50) value for the discriminative stimulus effects of the (-)-enantiomer was approximately 60-fold lower than the highest inactive doses of (+)-cocaine examined. In contrast, toxic effects were obtained with both enantiomers of cocaine, with (-)-cocaine approximately 8- or 13-fold more potent than its enantiomer in producing convulsions and lethality, respectively. These results indicate that there is a marked stereoselectivity in the psychomotor stimulant effects of cocaine, and additionally, that this stereoselectivity does not carry over to the toxic effects of cocaine, which appear to be mediated by different mechanisms.