Showing papers by "Andreas Pfeiffer published in 1986"

Psychotomimesis mediated by kappa opiate receptors.

Abstract: 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 sigma-phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at sigma-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 mu agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.

Anterior Pituitary Hormone Responses to a κ-Opioid Agonist in Man

Abstract: The present study was designed to investigate pituitary hormone responses to a κ-opiate receptor agonist in man. Normal men were given the racemic benzomorphan κ-agonist MR 2033 or its levorotatory isomer MR 2034 iv. Plasma levels of PRL and GH markedly increased after injection of 3.5 μg/kg MR 2033 or 1.9 or 3.8 μg/kg MR 2034. These effects of MR 2033 were blocked by the opiate antagonist naloxone (10 mg), thereby demonstrating their mediation by opiate receptors. The κ-agonist did not change plasma levels of LH and FSH. The secretion of TSH was significantly suppressed by MR 2033 and MR 2034, but this action was not antagonized by pretreatment with naloxone. The suppression of plasma TSH was, however, stereospecific since the (C)-isomer, MR 2035, did not affect TSH secretion. These data indicate that κ-opiate receptors are located on neuronal pathways regulating GH, TSH, and PRL secretion. The pattern of pituitary responses elicited by the κ-agonist differs from that of μ-opioid agonists, indicating dif...

Effects of a kappa-opioid agonist on adrenocorticotropic and diuretic function in man.

Abstract: Although kappa-opiate receptors represent an important fraction of the total opiate receptor capacity in human brain their endocrine function is unknown. We determined the effects of a kappa-opiate receptor agonist on the secretion of vasopressin, ACTH and cortisol and on diuresis. The racemic benzomorphan kappa agonist MR 2033 or its opiate active (-)-isomer, MR 2034, inhibited the release of cortisol and ACTH in 12 trials in a naloxone reversible manner; plasma levels of vasopressin were not altered. The (+)-isomer, MR 2035, did not affect the secretion of cortisol or ACTH. Surprisingly, in five other subjects large increases were observed in vasopressin, ACTH and cortisol following the kappa-agonist, which were probably elicited indirectly by aversive effects of the opioid. The subjects in whom vasopressin release was not altered by MR 2033 and MR 2034 displayed large decreases in urine osmolality which were not antagonized by naloxone. The opiate inactive (+)-isomer, MR 2035, caused no diuretic response. Subjects in whom vasopressin release was stimulated did not show decreases in urine osmolality indicating that vasopressin is capable of antagonizing the diuretic action of the kappa-agonist. Our data show that a kappa-agonist inhibits secretion of cortisol and ACTH by acting at stereospecific opiate receptors and elicits diuresis by acting at stereospecific, but naloxone-insensitive non-classical opioid receptors. These data support the concept that different types of kappa-receptors can be distinguished in man.