REVERSIBLE BINDING OF NALOXAZINE AND 14-HYDROXYDIHYDROMORPHAZINE WITH OPIATE RECEPTORS

Snyder et al reported that naloxazine (NZI) was an irreversible ligand of opiate receptors. But, in the experiment reported here, it was found that after incubation (30℃, 15 min) of NZI (1×10^-5) with rat brain P₂ membrane preparation, repeated washing could restore completely the reactivity of opiate receptors. The antagonizing effect of NZI on the inhibition of electrically induced contraction of the longitudinal muscle of guinea-pig ileum (GPI) by morphine could also be eliminated by repeated washings. An N-methyl analog of naloxazine, 14-hydroxydihydromorphazine (HZI), is an agonist of opiate receptors. Both receptor binding and GPI experiments revealed that neither the latter compound nor NZI reacted with opiate receptors as irreversible ligand. The duration of analgesic action of HZI in mice was no longer than that of morphine, although, it's ED₅₀, 1.3 mg/kg (Hot-plate, i.p.), was smaller than that of morphine (3 mg/kg).