Neuromuscular blocking properties of suxamethonium and decamethonium in normal and myasthenic rat muscle.
Patients with myasthenia gravis (MG) have increased tolerance to the neuromuscular blocking properties of suxamethonium (SCh) and decamethonium (C10) and exhibit a reversal of the C10-induced block by neostigmine. The effects of these drugs were compared in forelimb flexor digitorum longus muscle from normal rats and from rats with experimental autoimmune myasthenia gravis (EAMG) to investigate the similarity of EAMG to MG. The depolarization induced by 1, 5, 10 and 25 microM SCh or C10 at the motor end-plates was significantly higher in normal than in EAMG muscle. However, both normal and EAMG end-plates responded in a similar qualitative manner to each drug. The depolarization produced by SCh was typically maintained until the drug was washed from the bath. The depolarization produced by C10 tended to decrease after reaching its peak despite continued application of the drug. With both drugs, miniature end-plate potential (MEPP) amplitude reduction is maintained until a saline wash. Neostigmine interaction with SCh and C10 in normal and EAMG muscle was compared by measuring isometric twitch tension in vitro. Neostigmine potentiated the neuromuscular block produced by either SCh or C10 in both normal and EAMG muscle. Thus muscle from rats with EAMG shares with MG an increased tolerance to SCh and C10 when compared to normal muscle but does not exhibit the qualitatively different interaction of C10 affected muscle with neostigmine that is found in MG patients. This and other studies comparing EAMG and MG indicate that EAMG is an appropriate model of MG but differences such as we have noted should be considered when extrapolating data from EAMG to the human disease.
Johnson, BR; Kim, YI; Sanders, DB
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