Butelman E R, Ko M C, Traynor J R, Vivian J A, Kreek M J, Woods J H
Laboratory on the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10021, USA.
J Pharmacol Exp Ther. 2001 Sep;298(3):1049-59.
GR89,696 is a synthetic kappa-opioid receptor agonist, recently reported to have an agonist profile consistent with selectivity at the proposed "kappa(2)" subtype. The present studies evaluated the effects of GR89,696 in vitro (i.e., in radioligand binding and [(35)S]guanosine-5'-O-(3-thio)triphosphate assays) and in vivo in rhesus monkeys, in assays used to study kappa-opioid agonists (i.e., thermal antinociception, sedation and muscle relaxation, diuresis, and increases in serum prolactin levels, as well as ethylketocyclazocine and U69,593 discrimination). Furthermore, the sensitivity of GR89,696 to naltrexone and nor-binaltorphimine (nor-BNI) antagonism was compared with that of U50,488 and U69,593, ligands selective for the proposed "kappa(1)" subtype. Overall, GR89,696 displayed the profile of a highly potent kappa-opioid agonist, following parenteral administration in rhesus monkeys. GR89,696 was less sensitive than U50,488 and U69,593 to naltrexone or nor-BNI antagonism, consistent with an action through the proposed kappa(2) receptor subtype.
GR89,696是一种合成的κ-阿片受体激动剂，最近有报道称其激动剂特征与对拟议的“κ(2)”亚型的选择性一致。本研究评估了GR89,696在体外（即放射性配体结合和[³⁵S]鸟苷-5'-O-(3-硫代)三磷酸试验）以及在恒河猴体内的作用，这些试验用于研究κ-阿片受体激动剂（即热镇痛、镇静和肌肉松弛、利尿以及血清催乳素水平升高，还有乙基酮环唑辛和U69,593辨别试验）。此外，还将GR89,696对纳曲酮和去甲二氢吗啡酮（nor-BNI）拮抗作用的敏感性与U50,488和U69,593（对拟议的“κ(1)”亚型具有选择性的配体）进行了比较。总体而言，在恒河猴经肠胃外给药后，GR89,696表现出高效κ-阿片受体激动剂的特征。GR89,696对纳曲酮或nor-BNI拮抗作用的敏感性低于U50,488和U69,593，这与通过拟议的κ(2)受体亚型发挥作用一致。
