Dantrolene

Dantrolene is an orally active, non-competitive glutathione reductase inhibitor with a K_i of 111.6 μM and an IC₅₀ of 52.3 μM. Dantrolene is also a calcium channel protein inhibitor. Dantrolene inhibits the release of Ca²⁺ from RyR1 and RyR3, which can be beneficial in a variety of pathologies caused by disruptions in calcium homeostasis (e.g., stroke, ischemia/reperfusion injury, and neurodegenerative diseases). Dantrolene offers relief of muscle spasms, malignant hyperthermia, and antitoxic, antipyretic, and anti-inflammatory properties^{[1][2][3][4][5][6][7][8][9][10][11]}. In Vitro: Dantrolene (50 μM) sodium alleviates malignant hyperthermia by preventing overactive Ca²⁺ release by increasing the affinity of ryanodine receptor (RyR) for Mg²⁺ in rat skin fibers^[2].
Dantrolene (30 μM, 1 h-3 days) sodium ameliorates the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca²⁺ homeostasis and physiological autophagy, cell survival and proliferation in induced pluripotent stem cells derived from patients with Alzheimer's disease ^[3].
Dantrolene (40 μM, 12 h) sodium enhances the protective effect of hypothermia on cerebral cortex neurons, including improved morphology, increased survival and mitochondrial membrane potential, decreased intracellular reactive oxygen species, cytoplasmic histone-associated DNA fragmentation and apoptosis^[7].
In Vivo: Dantrolene (5-20 mg/kg, i.v.) sodium exhibits cardioprotective effects in a rat model of Digoxin (HY-B1049)-induced cardiotoxicity^[4].
Dantrolene (5-10 mg/kg, i.p.) sodium attenuates spinal cord inflammation in mice with experimental autoimmune encephalomyelitis (EAE) ^[5].
Dantrolene (5 mg/kg, intranasal or subcutaneous, 3 times per week) sodium improves cognitive dysfunction in 5XFAD Alzheimer's disease (AD) mice ^[6].