| Abstract: |
On the basis of its in vivo activity and binding affinity, naloxone benzoylhydrazone has been characterized as a κ3-opioid receptor agonist and a μ-opioid receptor antagonist. This paper continues its pharmacological characterization with the help of isolated tissue preparations. Naloxone benzoylhydrazone was found to have partial agonist activity in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. As an antagonist, naloxone benzoylhydrazone is similar to naloxone, with pA2 values of 8.8, 7.8, and 7.8 for μ-, δ-, and κ1-opioid receptors, respectively. Its agonist activity in the guinea pig ileum preparation was not influenced by β-funaltrexamine treatment but was reversed by the selective κ-opioid receptor antagonist nor-binaltorphimine and by the irreversible κ1-opioid receptor blocker UPHIT (1S,2S)-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide. The presence of κ3-opioid receptors could not be demonstrated by [3H]naloxone benzoylhydrazone binding in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. From these studies it is concluded that the partial agonist activity of naloxone benzoylhydrazone in this bioassay is probably due to the activation of the κ1-opioid receptors. © 1995. |
| Keywords: |
controlled study; unclassified drug; nonhuman; mouse; animal; animal tissue; drug antagonism; brain; computer simulation; receptors, opioid, mu; receptor binding; ileum; muscle, smooth; in vitro; naloxone; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide; beta funaltrexamine; enkephalin[2,5 dextro penicillamine]; naltrexone; cyclohexanes; pyrrolidines; receptor subtype; binding, competitive; opiate antagonist; receptors, opioid, delta; naloxone benzoylhydrazone; kappa opiate receptor; opiate peptide; radioligand; guinea pig; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; narcotic antagonists; radioligand assay; opiate agonist; guinea pigs; agonist; norbinaltorphimine; smooth muscle contractility; myenteric plexus; male; priority journal; article; receptors, opioid, kappa; κ-opioid receptor; kappa opiate receptor antagonist; support, u.s. gov't, p.h.s.; n methyl n [7 (1 pyrrolidinyl) 1 oxaspiro[4.5]dec 8 yl]benzeneacetamide; partial agonist; ileum, guinea pig; 2 isothiocyanato 4,5 dichloro n methyl n [2 (1 pyrrolidinyl) cyclohexyl] benzeneacetamide; bremazocine; vas deferens
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