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Specific binding of 3H-naloxone to opiate receptors was found to be irreversibly inactivated by morphine. This inactivation exhibited pseudo-first-order kinetics. The presence of sulfhydryl compounds or morphine during incubation with morphinone proved good protection. Morphinone-pretreated mice blocked the analgesic effect of morphine. The possible mechanism for these observations is proposed as follows: morphinone binds covalently to sulfhydryl group of opiate receptors, and inactivates irreversibly opiate binding sites, thus blocking the analgesic effect of morphine.
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