CCB, a novel specific kappa opioid agonist, which discriminates between opioid and sigma 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 kappa opioid receptor types (Ki = 0.41 +/- 0.19 nM). In contrast to other kappa opioid agonists, CCB is also selective with respect to sigma 1 sites (Ki = 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 kappa opioid receptors.
Ronsisvalle
G
G
Institute of Pharmaceutical Chemistry, University of Catania, Italy.
Prezzavento
O
O
Pasquinucci
L
L
Marrazzo
A
A
Vittorio
F
F
Gomez-Vidal
J A
JA
Carboni
L
L
Spampinato
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D001667:Binding, Competitive; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000187:drug effects*
D000700:Analgesics; D001575:Benzomorphans; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine