NALOXAZONE, A LONG-ACTING OPIATE ANTAGONIST - EFFECTS ON ANALGESIA IN INTACT ANIMALS AND ON OPIATE RECEPTOR-BINDING INVITRO

  • 1 January 1980
    • journal article
    • research article
    • Vol. 214  (3) , 455-462
Abstract
Administration of naloxazone, a hydrazone derivative of naloxone, to intact mice produces a prolonged inhibition of in vitro [3H]opiate binding lasting up to 3 days. The effect is selective since naloxazone treatment produces no changes in .alpha.- or .beta.-adrenergic, muscarinic or benzodiazepine receptor binding and the effects on opiate binding sites are not reproduced by non-narcotic hydrazines. Scatchard analyses of saturation experiments 24 h after in vivo naloxazone treatment show an absence of high affinity binding sites of [3H]naloxone, [3H]dihydromorphine and 2-D-[3H]Ala-Met-enkephalinamide, but low affinity sites are relatively unaffected. Blockade of high affinity sites by naloxazone produces an 11-fold increase in the ED50 value for morphine analgesia at 24 h with both tail-flick and writhing assays. Naloxazone produces no change in the LD50 value for morphine. As high affinity binding returns to control levels over 3 days, the ED50 for morphine analgesia in naloxazone-pretreated mice returns to control values. Accordingly, the analgetic, but not lethal, effects of morphine may be mediated by the high affinity subpopulation of opiate receptors.