Levallorphan methyl iodide (SR 58002), a potent narcotic antagonist with peripheral selectivity superior to that of other quaternary compounds.

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.