Musculoskeletal Agents
Skeletal Muscle Relaxants

Description: Dantrolene is an oral and intravenous skeletal muscle relaxant. It is a hydantoin derivative. Dantrolene is the drug of choice for treating malignant hyperthermia. Although dantrolene is an effective skeletal muscle relaxant, baclofen is preferred for some patients because of dantrolene's risk of causing hepatotoxicity. Dantrolene was approved for use by the FDA in January 1974.

Mechanism of Action: Dantrolene's mechanism of action differs from that of other oral skeletal muscle relaxants. Dantrolene is believed to decrease muscle contraction by directly interfering with calcium ion release from the sarcoplasmic reticulum within skeletal muscle cells. This "uncouples" the excitation-contraction process, making dantrolene useful in treating malignant hyperthermia. Dantrolene does not interfere with calcium entry at the cell surface as do verapamil and other calcium-channel inhibitors. Dantrolene has little or no effect on cardiac or smooth muscle at doses used for skeletal muscle relaxation. The extent of its CNS effect is not known.

Clinically, dantrolene is used to treat malignant hyperthermia and upper motor neuron disorders. In upper motor neuron disorders, dantrolene attenuates muscle response to direct stimulation, monosynaptic, and polysynaptic reflexes. The drug produces generalized, mild weakness of skeletal muscles and overall improvement in muscle tone.

Pharmacokinetics: Dantrolene is administered orally and intravenously. After oral administration, 35% of a dose is absorbed, and peak concentrations are reached within 5 hours. Therapeutic effects in patients being treated for upper motor neuron disorders may not be apparent for a week or longer. The drug is highly bound to plasma proteins, primarily albumin. Dantrolene is hepatically metabolized to less active and inactive metabolites. The half-life is approximately 9 hours in healthy adults and about 7.3 hours in children. Metabolites are eliminated renally.

Drug Information Provided by
Gold Standard, Inc. � 2007

Dantrolene, a hydantoin derivative, directly interferes with muscle contraction by binding the Ryr1 receptor calcium channel and inhibiting calcium ion release from the sarcoplasmic reticulum. This intracellular dissociation of excitation–contraction coupling contrasts with the depolarizing and nondepolarizing muscle relaxants that antagonize the extracellular neuromuscular junction. The dose is 2.5 mg/kg intravenously every 5 min until the episode is terminated. The upper limit of dantrolene therapy is generally 10 mg/kg. Dantrolene is packaged as 20 mg of lyophilized powder to be dissolved in 60 mL of sterile water. Depending on the dose required, reconstitution can be time consuming. The effective half-life of dantrolene is about 6 h. After initial control, dantrolene 1 mg/kg intravenously is recommended every 6 h for 24–48 h to prevent relapse because MH can recur within 24 h. It should be noted that dantrolene is not specific for MH; it also decreases temperature in thyroid storm and neuroleptic malignant syndrome. Dantrolene is a relatively safe drug. Although chronic therapy for spastic disorders has been associated with hepatic dysfunction, the most serious complication following acute administration is generalized muscle weakness that may result in respiratory insufficiency or aspiration pneumonia. Dantrolene can cause phlebitis in small peripheral veins and should be given through a central venous line if one is available. The safety and efficacy of dantrolene call for its immediate use in this potentially life-threatening disease.