Dantrolene sodium (Dantrium) is a hydantoin derivative. It acts directly on muscle contractile elements, decreasing the release of calcium from skeletal muscle sarcoplasmic reticulum and thereby interfering with the excitation-contraction coupling needed to contract muscles.61–63
The effect is most pronounced on extrafusal fibers, but a minor effect also is seen on intrafusal fibers. Whether this effect may alter spindle sensitivity is unclear.64
Dantrolene has a greater effect on fast-twitch fibers (those that produce rapid contraction and high tension but fatigue relatively easily) than on slow-twitch fibers (those that contract tonically, producing less tension, but are more resistant to fatigue).65
Placebo-controlled trials of dantrolene demonstrated significant reduction of muscle tone and hyperreflexia.63,66–68 In a double-blind crossover design in 42 patients with multiple sclerosis (MS), both dantrolene and diazepam decreased spasticity, clonus, hyperreflexia, muscle stiffness, and cramping.69
In children with cerebral palsy70 and in patients with spasticity due to various cerebral and spinal disorders,71 studies found that spasticity was slightly better controlled and side effects more tolerable with dantrolene than with diazepam.
The half-life for oral dantrolene is approximately 15 hours, with peak concentrations occurring in 3 to 6 hours. It is metabolized mainly by the liver.
Dantrolene is initiated at 25 mg per day and should be increased slowly, in increments of 25 mg per day every 5 to 7 days. The recommended maximum dosage is 400 mg per day in divided doses.
Because its site of action is peripheral, the most common side effect of dantrolene is weakness, the mechanism by which it mediates its antispasticity action. For this reason, dantrolene may be most appropriate for nonambulatory patients with severe spasticity. Other side effects include drowsiness, diarrhea, and malaise.
Hepatotoxicity—which can be irreversible—is the major concern with dantrolene sodium, so liver function tests should be evaluated before the initiation of therapy and every 3 months thereafter.23
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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