CCB, a novel specific κ opioid agonist, which discriminates between opioid and σ 1 recognition sites

CCB, 6,11 -Dimethyl-1,2,3,4,5,6-hexahydro-3-{[2′-methoxycarbonyl-2′-(4-chlorophenyl) cyclopropyl]methyl}-2,6-methano-3-benzazocin-8-ol, displays specificity and very high affinity for κ opioid receptor types (K 1 = 0.41 ± 0.19 nM). In contrast to other κ opioid agonists, CCB is also selective with respect to σ 1 sites (K 1 = 1,050 ± 55 nM). CCB displays antinociceptive and sedative effects in the mouse comparable to those of U50,488H and morphine. Naltrexone fully antagonizes these effects. The sedative effects of CCB are blocked in mice pretreated with naltrexone or nor-BNI. CCB and U50,488H produce a superimposable diuresis in rats. Naltrexone and nor-BNI, both are effective in antagonizing the effect. CCB does not produce any stereotyped behavior or ataxia in the behavioral 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 κ opioid receptors.