Inhibition of acetylcholinesterase by various opioids

The anti-acetylcholinesterase (AChEase) activity of 15 opioids, namely morphine, nalorphine, oxymorphone, naloxone, naltrexone, N-methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo-methadone, dextro-methadone, pethidine, leu-enkephalin and U-50,488H was investigated. Among the opioids, the morphinans (in terms of their dissociation constants) are the strongest inhibitors of the enzyme. These are followed by the phenanthrenes and the morphones, though two members of the latter group are non-inhibitors. Levo-methadone, dextro-methadone, pethidine and leu-enkephalin are also non-inhibitors of the enzyme. The present results, together with our previous findings, support the suggestion that opioids which are poor or non-inhibitors of AChEase are strong inhibitors of the ACh-induced contraction of the toad rectus, whereas the reverse is true for inhibitors of AChEase.