阿片受体不可逆性部分激动剂A-α-CAO的药理学研究

Pharmacological study of an irreversible partial agonist of opiate receptors, A-alpha-CAO.

作者信息

Li M X, Li L Y, Li B B, Jin Y H, Qiu Z B, Zhu C L

机构信息

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing.

出版信息

Sci China B. 1989 Mar;32(3):335-46.

PMID:2551335

Abstract

A-alpha-CAO induces weak analgesia with very short duration in mice and is able to antagonize the analgesic effect of morphine (Mor) up to 3-4 days after a single injection. No tendency of dependence has been observed. It acts as a partial agonist on MVD with Ke value of 9 X 10(-9) mol/L. Its antagonist effect remains after several washes and its agonist effect cannot be reversed by naloxone (Nx), provided the incubation time or the concentration of the agent is sufficient. On isolated GPI, A-alpha-CAO is a pure agonist with IC50 of 5.7 X 10(-10) mol/L; this agonist effect cannot be removed by washing but can be reversed by Nx. On RVD and RbVD, it has antagonist effect against beta-endorphine (beta-end) and U50488H, which cannot be washed out easily, and the pA2 are 7.5 and 7.6 respectively. A-alpha-CAO also inhibits the specific binding of 3H-etorphine (3H-Etor) to the P2 fraction of the mouse brain membrane with an IC50 of 3.2 X 10(-9) mol/L. The inhibition on the high affinity binding sites of 3H-Etor remains 95% even after 6 washes.

摘要

A-α-CAO在小鼠中诱导出作用持续时间非常短的弱镇痛作用，并且在单次注射后长达3 - 4天能够拮抗吗啡（Mor）的镇痛效果。未观察到依赖性倾向。它在μ阿片受体（MVD）上作为部分激动剂起作用，Ke值为9×10⁻⁹ mol/L。经过几次冲洗后其拮抗作用仍然存在，并且只要孵育时间或药物浓度足够，其激动作用不能被纳洛酮（Nx）逆转。在离体的中脑导水管周围灰质（GPI）上，A-α-CAO是一种纯激动剂，IC50为5.7×10⁻¹⁰ mol/L；这种激动作用不能通过冲洗去除，但可以被Nx逆转。在孤束核尾侧亚核（RVD）和迷走神经背核（RbVD）上，它对β-内啡肽（β-end）和U50488H具有拮抗作用，这种作用不容易被冲洗掉，pA2分别为7.5和7.6。A-α-CAO还抑制³H-埃托啡（³H-Etor）与小鼠脑膜P2组分的特异性结合，IC50为3.2×10⁻⁹ mol/L。即使经过6次冲洗，对³H-Etor高亲和力结合位点的抑制仍保持95%。