CCB, A NOVEL SPECIFIC KAPPA-OPIOID AGONIST, WHICH DISCRIMINATES BETWEEN OPIOID AND SIGMA(1) RECOGNITION SITES

CCB, ,2,3,4,5,6-hexahydro-3-{[2'-methoxycarbonyl-2'-(4- cyclopropyl]me thyl}-2,6-methano-3-benzazocin-8-ol, displays specificity and very hig h affinity for kappa opioid receptor types (K-i = 0.41+/-0.19 nM). In contrast to other kappa opioid agonists, CCB is also selective with re spect to sigma(1) sites (K-i = 1,050+/-55 nM). CCB displays antinocice ptive and sedative effects in the mouse comparable to those of U50,488 H and morphine. Naltrexone fully antagonizes these effects. The sedati ve effects of CCB are blocked in mice pretreated with naltrexone or no r-BNI. CCB and U50,488H produce a superimposable diuresis in rats. Nal trexone and nor-BNI, both are effective in antagonizing the effect. CC B does not produce any stereotyped behavior or ataxia in the behaviora l assay in doses up to 40 mg/kg s.c.. These findings suggest that CCB might be a useful tool to investigate the physiological role of kappa opioid receptors.