Supersensitivity to neostigmine and resistance to d-tubocurarine in mice with hereditary myopathy

¹ Radioisotope Service and Neurology Section, Veterans Administration Center; and Departments of Physiological Chemistry and Medicine, University of California Medical Center, Los Angeles, California

Mice having a hereditary myopathy (dystrophia muscularis) and normal controls were injected with neostigmine and/or d-tubocurarine. Neostigmine (8–19 µg/kg, i.v.) either induced or increased tremors in 16 of a group of 18 myopathic mice. Only 1 of 27 normal mice showed any twitching after the same treatment. Neostigmine when given intraperitoneally in larger doses (21–37 µg/kg) failed to produce twitching in either myopathic or normal mice if the animals were less than 4 weeks old. However, in mice of ages >30 days intraperitoneally administered neostigmine (7 g-18 µg/kg) did produce twitching in dystrophics (12/12) but not in most normals (1/12). A dose of d-tubocurarine (200–250 µg/kg, i.v.), which caused death in 78% of nine normal mice, was lethal to only 22% of nine myopathic mice. The data suggest that muscle from the myopathic mice may share with denervated muscle the property of supersensitivity to acetylcholine.