Psychotomimesis Mediated by kappa Opiate Receptors

The kappa opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the kappa agonist cyclazocine are thought to be mediated by an action at σ -phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at σ -phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, kappa opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of μ agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.