title: Allylprodine analogues as receptor probes. Evidence that phenolic and nonphenolic ligands interact with different subsites on identical opioid receptors.
abstract: The m-hydroxy analogues of allylprodine and related structures have been synthesized and tested for narcotic agonist and antagonist activity on the electrically stimulated guinea pig ileum and by the hot-plate procedure in mice. It has been found that m-hydroxyallylprodine (alpha-2) is neither an agonist nor antagonist. Other phenolic congeners similarly have little or no activity. The fact that these results are in dramatic contrast with the structure-activity profile of morphine and closely related opiates has led to the proposal that the interaction of morphine and allylprodine (alpha-1) with the mu opioid receptor differs. This difference is postulated to arise from the recognition of the aromatic groups of morphine and alpha-1 by different aromatic-binding subsites of the receptor. These subsites are suggested to be identical with those which recognize the aromatic rings of the Tyr1 and Phe4 of the enkephalins and endorphins. A receptor model consistent with these results is proposed.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009292:Narcotic Antagonists; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis*; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D009292:Narcotic Antagonists; D010636:Phenols; D010880:Piperidines; D011957:Receptors, Opioid; D009020:Morphine