Naloxonazine actions in vivo

Naloxonazine is a relatively selective mu 1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for mu 1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistant inhibition of binding lasting 24 h which was relatively selective for mu 1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both mu 1 (naloxonazine-sensitive) and a non-mu 1 (naloxonazine-insensitive) components. The ratio of mu 1 to non-mu 1 analgesia was greater at low morphine doses, implying that morphine activated mu 1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively mu 1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than mu 1.