morphinans and naloxazone

Topics: Analgesics, Opioid; Constipation; Humans; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; Polyethylene Glycols; Quaternary Ammonium Compounds

Receptor binding experiments with masking of mu- and delta-receptors in the presence of an excess of unlabelled dihydromorphine and [D-Ala2, D-Leu5]enkephalin have been carried out. They indicate that 12 to 17% of original high affinity binding of [3H]Mr 2034 [-)(1R,5R,9R,2"S)-5,9-dimethyl-2-tetrahydrofurfuryl-2'-hydroxy-6, 7-benzomorphan hydrochloride), an opioid kappa-agonist, could then be detected as kappa-receptor sites in brain membranes both from untreated rats and from rats pretreated with naloxazone, too. Because of the irreversible blockade of the high affinity binding sites by naloxazone (naloxone hydrazone) treatment, the masking effects of mu- and delta-selective ligands seem to be mediated by the low affinity binding sites of these opioid receptor types. As could be shown before with [3H]Mr 2034, another kappa-agonist, [3H]bremazocine does not seem to be affected in its binding properties by naloxazone treatment of the rat in vivo. Displacement studies with several opioid agonists and antagonists, [3H]Mr 2034 and [3H]ethylketocyclazocine as radioligands in brain membranes from naloxazone treated rats and untreated controls provided further support for the evidence of two different kappa-receptors.

Topics: Animals; Benzomorphans; Binding, Competitive; Cyclazocine; Dihydromorphine; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Ethylketocyclazocine; In Vitro Techniques; Kinetics; Male; Morphinans; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, kappa

Saturation binding studies with [3H]Mr 2034, an opioid kappa-agonist, were carried out using brain homogenates from naloxazone-pretreated rats (200 mg/kg subcutaneously 16 hours before killing). [3H]Mr 2034 showed unaffected binding characteristics, compared to membrane homogenates of untreated controls. However, in contrast to this finding, naloxazone blocked the high affinity binding of other tritiated opioid agonists and antagonists, among them the kappa-agonist [3H]ethylketocyclazocine. Displacement studies with [3H]dihydromorphine, [3H]ethylketocyclazocine and [3H]Mr 2034 in brain membrane homogenates from untreated rats and using various opioid agonists and antagonists indicated that these substances are capable of differentiating between the two kappa-ligands [3H]ethylketocyclazocine and [3H]Mr 2034, too.

Topics: Animals; Benzomorphans; Binding, Competitive; Brain; Cyclazocine; Ethylketocyclazocine; In Vitro Techniques; Kinetics; Morphinans; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, kappa