THE IN-VITRO PHARMACOLOGICAL CHARACTERIZATION OF NALOXONE BENZOYLHYDRAZONE

On the basis of its in vivo activity and binding affinity, naloxone be nzoylhydrazone has been characterized as a kappa(3)-opioid receptor ag onist and a mu-opioid receptor antagonist. This paper continues its ph armacological characterization with the help of isolated tissue prepar ations. Naloxone benzoylhydrazone was found to have partial agonist ac tivity in the guinea pig ileum longitudinal muscle/myenteric plexus pr eparation. As an antagonist, naloxone benzoylhydrazone is similar to n aloxone, with pA(2) values of 8.8, 7.8, and 7.8 for mu-, delta-, and k appa(1)-opioid receptors, respectively. Its agonist activity in the gu inea pig ileum preparation was not influenced by beta-funaltrexamine t reatment but was reversed by the selective kappa-opioid receptor antag onist nor-binaltorphimine and by the irreversible kappa(1)-opioid rece ptor blocker UPHIT rans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-( 1-pyrrolidinyl)-cyclohexyl] benzeneacetamide. The presence of kappa(3) -opioid receptors could not be demonstrated by [H-3]naloxone benzoylhy drazone binding in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. From these studies it is concluded that the partia l agonist activity of naloxone benzoylhydrazone in this bioassay is pr obably due to the activation of the kappa(1)-opioid receptors.