Naloxazone Explained

Naloxazone should not be confused with Naloxone.

Naloxazone is an irreversible μ-opioid receptor antagonist which is selective for the μ₁ receptor subtype.^[1] Naloxazone produces very long lasting antagonist effects as it forms a covalent bond to the active site of the μ-opioid receptor,^[2] thus making it impossible for the molecule to unbind and blocking the receptor permanently until the receptor is recycled by endocytosis.

Naloxazone is the hydrazone analog of naloxone. It has been reported that naloxazone is unstable in acidic solution, dimerizing into the more stable and much more potent antagonist naloxonazine via the free NH₂ of the hydrazone to form an azine linkage.^[3] Under conditions in which no naloxonazine formation could be detected, naloxazone did not display irreversible μ opioid receptor binding.^[3]

See also

• Chlornaltrexamine, an irreversible mixed agonist-antagonist
• Oxymorphazone, an irreversible μ-opioid full agonist

Notes and References

1. 10.1126/science.6245448. 6245448. Opiate analgesia: Evidence for mediation by a subpopulation of opiate receptors. Science. 208. 4443. 514–6. 1980. Pasternak. G.. Childers. Snyder. S.. 1980Sci...208..514P.
2. 10.1016/0014-2999(86)90333-X. 3021478. Naloxonazine actions in vivo. European Journal of Pharmacology. 129. 1–2. 33–8. 1986. Ling. Geoffrey S.F.. Simantov. Ronit. Clark. Janet A.. Pasternak. Gavril W..
3. 10.1016/0024-3205(82)90387-3. 6292633. Naloxonazine, a potent, long-lasting inhibitor of opiate binding sites. Life Sciences. 31. 12–13. 1385–8. 1982. Hahn. Elliot F.. Pasternak. Gavril W..