Dantrolene-d4 is intended for use as an internal standard for the quantification of dantrolene by GC- or LC-MS. Dantrolene is an inhibitor of calcium release from the sarcoplasmic reticulum (IC50 = 0.3 μM).1 It binds to sarcoplasmic reticulum vesicles isolated from normal and malignant hyperthermia-susceptible (MHS) pigs with Kd values of 0.3 and 0.09 μM, respectively. Dantrolene reduces spontaneous calcium wave frequency and amplitude in the presence of calmodulin in isolated mouse cardiomyocytes with IC50 values of 0.42 and 0.19 μM, respectively.2 It reduces the magnitude of electrically stimulated twitch tensions in isolated rat extensor digitorum longus and soleus muscles (IC50 = 3 μg/ml) and MHS pigs (ED50 = 0.85 mg/kg).3,4. Formulations containing dantrolene have been used in the treatment of malignant hyperthermia.
|1. Kobayashi, S., Yano, M., Suetomi, T., et al. Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J. Am. Coll. Cardiol. 53(21), 1993-2005 (2009).|2. Oo, Y.W., Gomez-Hurtado, N., Walweel, K., et al. Essential role of calmodulin in RyR inhibition by dantrolene. Mol. Pharmacol. 88(1), 57-63 (2015).|3. Kotsias, B.A., and Muchnik, S. Reversible effect of dantrolene sodium on twitch tension of rat skeletal muscle. Arch. Neurol. 35(4), 234-236 (1978).|4. Nelson, T.E., and Flewellen, E.H. Rationale for dantrolene vs. procainamide for treatment of malignant hyperthermia. Anesthesiology 50(2), 118-122 (1979).