title: Levallorphan methyl iodide (SR 58002), a potent narcotic antagonist with peripheral selectivity superior to that of other quaternary compounds.
abstract: The peripheral selectivity of the newer quaternary narcotic antagonist levallorphan methyl iodide (SR 58002) was found superior in mice to those of the previously available compounds N-allyl levallorphan (CM 32191), N-methyl nalorphine (MNph) and N-methyl naloxone (MNx). SR 58002 and MNph were the most potent (ID50, mg/kg s.c., 3.6 and 3.7) in preventing constipation by s.c. morphine (charcoal meal). Antinociception (hot-plate) of s.c. morphine was completely prevented by MNx, MNph and CM 32191 (ID50, mg/kg s.c., 1.6, 8.6 and 15.2) but only partially antagonized by 30 mg/kg s.c. SR 58002. Constipation elicited centrally by intracerebroventricular (i.c.v.) morphine was prevented by either s.c. MNx or MNph but not by SR 58002 or CM 32191, up to 60 mg/kg.
mesh_terms: D000818:Animals; D003248:Constipation / Q000503:physiopathology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007977:Levallorphan / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007977:Levallorphan; D009270:Naloxone; C045482:N-methyllevallorphan; D009020:Morphine