Differential effects of ketamine isomers on neuronal and extraneuronal catecholamine uptake mechanisms

Contractile responses of isolated rabbit aortic strips to epinephrine and norepinephrine were potentiated in a dose-related manner by (+) ketamine but not by (-) ketamine (1.1 X 10(-5) M - 3.7 X 10(-4) M). Potentiation was blocked completely by pretreatment with the extraneuronal uptake inhibitor cortisol (83-138 microM) but was unaffected by the neuronal uptake inhibitor cocaine (29 microM). Responses of the rat anococcygeus muscle to these catecholamines were potentiated by both isomers, with (+) ketamine being more potent than its optical antipode. These effects were blocked completely in tissues from 6-hydroxydopamine sympathectomized animals. Results suggest that inhibition of extraneuronal uptake of catecholamines by racemic ketamine is due solely to an action of the (+) isomer, whereas both isomers appear capable of inhibiting neuronal uptake.