[Molecular basis of pharmacological action of irreversible opioid receptor agonist alpha-CAO]

Molecular mechanism of opioid effect was studied in mouse brain using alpha-CAO (7 alpha-N, N-Bis (beta-chloroethyl)amino-6, 14-endo-ethenotetrahydrooripavine), 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 alpha-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 alpha-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.