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Dantrolene is a hydantoin derivative which is structurally similar to both anticonvulsants and local anaesthetics, but does not possess their properties. It inhibits the release of calcium from skeletal muscle sarcoplasmic reticulum, dissociating excitation -contraction coupling. It has no effect on either smooth or cardiac muscle.
The most important use of dantrolene is to treat malignant hyperthemia. It is also sometimes employed in the control of fever in thyrotoxicosis. Dantrolene has also been used in the treatment of the following conditions with varying degrees of success: heatstroke, neuroleptic malignant syndrome, MAOI overdose, amphetamine overdose, and organophosphate poisoning. It has also been tried as an antispastic agent for skeletal muscle.
Dantrolene can be administered orally or intravenously. About 70% of the oral dose is absorbed, and the peak blood level is reached around 5 hours postingestion. It is metabolised in the liver to 5-hydroxydantrolene, and upto 25% is excreted in the urine as the hydroxy metabolite.
Overdose results in muscle weakness, visual disturbances, lethargy, nausea, vertigo, pulmonary oedema, convulsions, hepatic toxicity (hepatitis), aplastic anaemia and leukopenia. Pericarditis has been reported in patients on chronic dantrolene therapy. Hepatotoxicity has been reported as an idiosyncratic reaction to therapeutic doses of dantrolene.
Treatment involves symptomatic and supportive measures.
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