dantrolene

Dantrolene is a skeletal muscle relaxant that inhibits excitation–contraction coupling by blocking calcium release from the sarcoplasmic reticulum in skeletal muscle. It acts on the ryanodine receptor type 1 (RYR1) to reduce intracellular calcium, thereby decreasing muscle contraction. It has little to no effect on cardiac or smooth muscle.

Its principal clinical use is in the prevention and treatment of malignant hyperthermia, a potentially fatal reaction to certain anesthetic agents and depolarizing muscle relaxants. In an MH crisis, dantrolene is given intravenously to halt the hypermetabolic process. It is also used, with varying evidence, as prophylaxis in patients with known susceptibility and, less commonly, for other conditions such as severe spasticity or neuroleptic malignant syndrome in some settings.

For malignant hyperthermia, the typical initial intravenous dose is 1–2 mg/kg, repeated as needed up to a cumulative dose around 10 mg/kg, with dosing guided by clinical response. Dantrolene is supplied as dantrolene sodium for IV use, and an oral formulation is used for long-term management of spasticity, usually starting at 25 mg four times daily and titrating upward while monitoring liver function. Total daily doses commonly range from about 200–800 mg, depending on response and tolerance.

Dantrolene is poorly water-soluble and is extensively metabolized in the liver, with the half-life varying and potentially prolonged in hepatic impairment. Adverse effects include hepatotoxicity, especially with long-term use; drowsiness, dizziness, weakness, nausea, diarrhea, and phlebitis at IV injection sites. Rare hypersensitivity reactions may occur.