CI‐977, a novel and selective agonist for the κ‐opioid receptor

• DOI: 10.1111/j.1476-5381.1990.tb12110.x
• Publication Date: 2012-07-20T10:00:14Z
• Authors: J.C. Hunter; G.E. Leighton; K.G. Meecham; S.J. Boyle; D.C. Horwell; D.C. Rees; J. Hughes
• Keywords: DAMGO; Vas deferens

CI‐977 is a new, nonpeptide κ‐opioid compound that has been synthesized and its pharmacological properties determined in series of vitro vivo rodent models. In radioligand binding studies, with guinea‐pig forebrain homogenates, bound high affinity to [ 3 H]‐U69593‐labelled κ‐sites ( K i = 0.11 n m ) but low H]‐[ d ‐Ala 2 , MePhe 4 Glyol 5 ] enkephalin (DAMGO) labelled μ‐sites 99n ‐Pen 2,5 ]enkephalin (DPDPE) δ‐sites 1.04 μ ). also negligible H]‐(+)‐3‐(1‐propyl‐3‐piperidinyl)phenol (3‐PPP) σ‐sites 1.9 H]‐1‐(1‐[2‐thienyl]cyclohexyl)piperidine (TCP) PCP sites > 10 produced potent inhibition the electrically‐evoked contractions ileum rabbit vas deferens IC 50 values 0.087 nM 3.3 nM, respectively. The pK B for opioid antagonists naloxone (7.6) norbinaltorphimine (10.5) supported κ nature CI‐977‐mediated effects smooth muscle assays. was antinociceptive agent against mechanical noxious stimulus rats following intravenous, intramuscular, subcutaneous oral administration. effective chemical stimuli mouse ineffective thermal stimulus. by were completely reversed (1 mg kg −1 s.c.). At doses close those required produce antinociception, caused naloxone‐reversible diuresis locomotor activity. profile demonstrates it selective agonist at receptor.