Neuromuscular effects of some opioid agonists and antagonists

The effects of morphine, pethidine, (-) naloxone, N-methylnaloxone, naltrexone and levallorphan on acetylcholine-induced contraction of the toad rectus were studied. The drugs were shown to inhibit the contraction, and their inhibitory effect was suggested to be partly mediated via a peripheral opiate binding site. The depression of acetylcholine-induced contraction by levallorphan and dextrallorphan might indicate possible involvement of stereospecific binding sites, as the latter required a significantly higher concentration to produce the same magnitude of depression. Statistical analysis of the slope of the computer-plotted dose-response of acetylcholine in the presence and absence of each of the opioids indicates that these drugs can be classified into four categories. Morphine and naltrexone each formed a class of its own; (-) naloxone, N-methylnaloxone and pethidine formed another class; levallorphan and dextrallorphan formed the fourth class. The classification of the opioids into four categories reveals the possible existence of multiple opiate binding sites on the skeletal muscle. The significance of each of the sub-types of binding sites in the contraction of skeletal muscle and the mechanism by which it affects the contraction remains to be investigated.