Apparent efficacy of kappa-opioid receptor ligands on serum prolactin levels in rhesus monkeys

These studies investigated whether serum prolactin levels could be a quanti tative marker of the apparent efficacy of K-opioid receptor ligands in prim ates. The effects of s.c. bremazocine and U50,488 (trans-(+/-)-3,4-Dichloro -N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide; agonists), na lorphine (partial agonist) and nalmefene (antagonist) on prolactin levels w ere studied in intact female rhesus monkeys. The above compounds, except na lmefene, increased prolactin levels, and their actions conformed to sigmoid al dose-effect curves. The rank order of the compounds' maximum effects in this neuroendocrine endpoint is similar to that in cloned K-receptors in vi tro, and in a presently studied thermal antinociception assay in vivo. Prol actin may therefore be a quantitative marker of the apparent efficacy of K- opioid receptor ligands in primates. (C) 1999 Elsevier Science B.V. All rig hts reserved.