Studies on normal human skeletal muscle in relation to the pathopharmacology of malignant hyperpyrexia.
1. The effects of dantrolene on pharmacologically-induced contractures and potentiated isometric twitches in normal human skeletal muscle have been studied in vitro. 2. Dantrolene sodium, at concentrations of 3 mumol/l or less, attenuates basal twitch, inhibits halothane potentiation of basal twitch and inhibits halothane-potentiated potassium contractures, but has less effect on twitch potentiation by 2 mmol/l caffeine. 3. Caffeine contractures are attenuated by dantrolene concentrations of 12 mumol/l or greater. The effect of dantrolene on caffeine contracture is characterized by decreased contracture tension and by prolonged time to peak contracture. 4. The results indicate that halothane and 2 mmol/l caffeine have agonistic effects on the excitation-contraction (E-C) coupling mechanism, and suggest that they may act at separate E-C coupling sites. The relationships of these findings to the pathopharmacology of malignant hyperpyrexia are discussed.
D002110:Caffeine / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology
D002110:Caffeine; D003620:Dantrolene; D011188:Potassium; D006221:Halothane