Opiate Analgesia: Evidence for Mediation by a Subpopulation of Opiate Receptors

Naloxazone, a hydrazone derivative of the opiate antagonist naloxone, has a high affinity for opiate receptor binding sites. Naloxazone injections reduce opiate receptor binding to extensively washed mouse brain membranes for more than 24 hours, suggesting that the effect is irreversible. High-affinity binding sites are abolished by this treatment, whereas low-affinity sites are unaffected. Naloxazone treatment blocks the analgesic effects of morphine for at least 24 hours but does not prevent death from high doses of morphine. Thus analgesic but nonlethal opiate effects may be mediated by the high-affinity subpopulation of opiate receptors.

[1]  P. Cuatrecasas,et al.  Multiple opiate receptors: different regional distribution in the brain and differential binding of opiates and opioid peptides. , 1979, Molecular pharmacology.

[2]  D. L. Larson,et al.  Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity. , 1979, Science.

[3]  P. Portoghese,et al.  6.beta.-[N,N-Bis(2-chloroethyl)amino]-17-(cyclopropylmethyl)-4,5.alpha.-epoxy-3,14-dihydroxymorphinan (chloranaltrexamine), a potent opioid receptor alkylating agent with ultralong narcotic antagonist activity , 1978 .

[4]  John Hughes,et al.  Endogenous opioid peptides: multiple agonists and receptors , 1977, Nature.

[5]  J. Thompson,et al.  The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. , 1976, The Journal of pharmacology and experimental therapeutics.

[6]  S. Snyder,et al.  Selective enhancement of [3H]opiate agonist binding by divalent cations. , 1975, Molecular pharmacology.

[7]  S. Snyder,et al.  Opiate receptor binding: Enzymatic treatments that discriminate between agonist and antagonist interactions , 1975 .

[8]  S. Snyder,et al.  Identification of novel high affinity opiate receptor binding in rat brain , 1975, Nature.

[9]  S. Snyder,et al.  Differentiation of opiate agonist and antagonist receptor binding by protein modifying reagents , 1975, Nature.

[10]  S. Snyder,et al.  Opiate receptor binding: effects of enzymatic treatments. , 1974, Molecular pharmacology.

[11]  F. Wilcoxon,et al.  A simplified method of evaluating dose-effect experiments. , 1948, The Journal of pharmacology and experimental therapeutics.

[12]  Fred E. D'Amour,et al.  A METHOD FOR DETERMINING LOSS OF PAIN SENSATION , 1941 .