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THE EFFECT OF AZUMOLENE ON HYPERCONTRACTILITY AND SARCOPLASMIC RETICULUM CA2+‐DEPENDENT ATPASE ACTIVITY OF MALIGNANT HYPERPYREXIASUSCEPTIBLE PORCINE SKELETAL MUSCLE
Author(s) -
Foster P. S.,
Hopkinson K. C.,
Payne N.,
Denborough M. A.
Publication year - 1991
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1991.tb01482.x
Subject(s) - dantrolene , dantrolene sodium , caffeine , skeletal muscle , chemistry , malignant hyperthermia , contracture , halothane , endoplasmic reticulum , muscle contracture , endocrinology , medicine , muscle relaxant , calcium , atpase , sarcoplasm , pharmacology , anesthesia , biochemistry , anatomy , surgery , enzyme , organic chemistry
SUMMARY 1. Azumolene sodium is a new water‐soluble derivative of dantrolene sodium that also acts as a skeletal‐muscle relaxant. 2. Azumolene (6 μmol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)‐susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses. 3. Like dantrolene, azumolene (6 μmol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations. 4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine‐induced contractures, and the converse was also true. This was observed in both MH‐susceptible and control preparations. 5. Sarcoplasmic reticulum Ca 2+ ‐dependent ATPase activity from MH‐susceptible and control muscle was not affected by azumolene. 6. Like dantrolene, azumolene may inhibit Ca 2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.