Description
Dantrolene is an inhibitor of calcium release from the sarcoplasmic reticulum (IC
50 = 0.3 μM). It binds to sarcoplasmic reticulum vesicles isolated from normal and malignant hyperthermia-susceptible (MHS) pigs with K
d 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 IC
50 values of 0.42 and 0.19 μM, respectively. It reduces the magnitude of electrically stimulated twitch tensions in isolated rat extensor digitorum longus and soleus muscles (IC
50 = 3 μg/ml) and MHS pigs (ED
50 = 0.85 mg/kg). Formulations containing dantrolene have been used in the treatment of malignant hyperthermia.
Chemical Properties
mp 279-280C 3415821
Uses
Skeletal muscle relaxant;Blocker of Ca2+ release
Uses
Dantrolene Sodium Salt is a skeletal muscle relaxant, which inhibits intracellular Ca 2+release from the sarcoplasmic reticulum.
Definition
ChEBI: The anhydrous sodium salt of dantrolene.
brand name
Dantrium (Procter & Gamble).
Biological Activity
Inhibits release of Ca 2+ from sarcoplasmic reticulum via inhibition of ryanodine receptor (RYR) channels. Displays selectivity for RYR1 and RYR3 over RYR2. Protective against the effects of a variety of conditions and agents, including excitatory amino acids. Skeletal muscle relaxant and neuroprotectant.
References
[1] Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity
[2] A FRANDSEN A S. Mobilization of dantrolene-sensitive intracellular calcium pools is involved in the cytotoxicity induced by quisqualate and N-methyl-D-aspartate but not by 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate and kainate in cultured cerebral cortical neurons.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1992, 89 7: 2590-2594. DOI:
10.1073/pnas.89.7.2590[3] SUSANNE MUEHLSCHLEGEL J R S. Dantrolene: mechanisms of neuroprotection and possible clinical applications in the neurointensive care unit.[J]. Neurocritical Care, 2009, 10 1: 103-115. DOI:
10.1007/s12028-008-9133-4[4] SIMIN LU. A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014: E5292-301. DOI:
10.1073/pnas.1421055111
