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Overview
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Background
Dantrolene (sodium salt) is an antagonist of ryanodine receptor (RyR), with an IC50 of 5.9 ± 0.3 nM for RyR2 [1, 2].
RyRs are expressed on the surface of the endoplasmic reticulum and the sarcoplasmic reticulum, responsible for Ca2+ release from intracellular stores. Dysfunction of calcium homeostasis may lead to ischemia, hypoxia, seizure, trauma, anesthesia, and neurodegenerative diseases [1].
In mouse cardiomyocytes, dantrolene showed no effect on cardiac Ca2+ release in the absence of calmodulin, but reduced Ca2+ wave frequency (IC50 = 0.42 ± 0.18 µM, Emax = 47 ± 4%) and amplitude (IC50 = 0.19 ± 0.04 µM, Emax = 66 ± 4%) in the presence of 100 nM calmodulin, which implied that calmodulin was essential for dantrolene’s inhibition on RyRs [2].
In a mouse pancreatitis model induced by caerulein for 1 hour, dantrolene (5 mg/kg) reduced pancreatic trypsin activity by 59% and mitigated early ultrastructural derangements within the acinar cell. Eight hours after caerulein induction, dantrolene decreased pancreatic trypsin activity and serum amylase by 61 and 32%, respectively [3].[1]. Inan S, Wei H. The cytoprotective effects of dantrolene: a ryanodine receptor antagonist. Anesthesia & Analgesia, 2010, 111(6): 1400-1410.
[2]. Oo Y W, Gomez-Hurtado N, Walweel K, et al. Essential Role of Calmodulin in RyR Inhibition by Dantrolene. Molecular Pharmacology, 2015, 88(1): 57-63.
[3]. Orabi A I, Shah A U, Ahmad M U, et al. Dantrolene mitigates caerulein-induced pancreatitis in vivo in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2010, 299(1): G196-G204.
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