Differential Effects of Ketamine Isomers on Neuronal and Extraneuronal Catecholamine Uptake Mechanisms

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Abstract
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 .times. 10-5 M - 3.7 .times. 10-4 M). Potentiation was blocked completely by pretreatment with the extraneuronal uptake inhibitor cortisol (83-138 .mu.M) but was unaffected by the neuronal uptake inhibitor cocaine (29 .mu.M). 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.