阿片受体不可逆配体(α-CAO)药理作用的分子学基础

Molecular Basis of Pharmacological Action of Irreversible Opioid Receptor Agonist α-CAO

阿片受体不可逆配体(α-CAO)使小鼠大脑组织内cAMP含量呈双相变化,此变化分别与α-CAO给药初期的镇痛和持续作用后的成瘾效果相一致.进一步研究证明,在给予α-CAO急性期,见小鼠大脑组织中腺苷酸环化酶活性被抑制48％,且能被纳洛酮部分拮抗,在延迟相α-CAO能使小鼠大脑组织中AC活性显著增加,可能是产生成瘾作用机制之一.成瘾形成的调节因素可能是由于CaM含量的增加.

Molecular mechanism of opioid effect was studied in mouse brain using α-CAO(7α-N, N-Bis (β-chloroethyl) amino-6, 14-endo-ethenotetrahydroor-ipavine), an irreversible opioid receptor agonist. There was a biphasic response in cerebral cAMP content, including an initial sharp decline and a subsequent increase 3 days later, the response being in line with analgesic effect initiated by administration of α-CAO and development of habituation due to sustained drug administration. Further laboratory study indicated that in the acute stage, adenylate cyclase activity in the mouse brain was inhibited by 48% and the inhibitory effect was reversible by naloxone. The delayed effect of α-CAO in development of habituation was accompanied by increase of AC activity and cAMP content of the brain, calmodulin content in the brain. The later being also causative factor in development of habituation.