Dantrolene
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| 1-(((5-(4-nitrophenyl)-2-furanyl) methylene)amino)-2,4-imidazolidinedione | |
| CAS number 7261-97-4 or 14663-23-1 (dantrolene sodium) | ATC code M03CA01 |
| Chemical formula | C14H10N4O5 |
| Molecular weight | 336 |
| Bioavailability | 70% |
| Metabolism | Liver |
| Elimination half-life | 10-12 hours |
| Excretion | Bile, urine |
| Pregnancy category | C (USA) |
| Legal status | Unregulated |
| Routes of administration | oral capsules, intravenous |
Dantrolene sodium is a muscle relaxant that is currently the only specific and effective treatment for malignant hyperthermia. It is also used in the management of neuroleptic malignant syndrome, spasticity and ecstasy intoxication.
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Chemistry
Chemically it is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin.
The related substance azumolene is under development for similar indications. It has a bromine residue instead of the nitrite group, and is 30 times more water-soluble.
Mode of action
Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing intracellular calcium concentration.
Side-effects
Muscle weakness may persist for several days following treatment. It is potentially hepatotoxic.
Problems
The major problem with dantrolene is its poor water solubility, and ensuing difficulty rapidly preparing intravenous solutions in emergency situations. It is routinely mixed with mannitol to improve water solubility.
A minor problem with dantrolene is that the preparation is not cheap and only has a shelf life of 2 years. Smaller hospitals may not see a case of malignant hyperthermia for more than a decade at a time but will still routinely order dantrolene just in case a case arises.
Reference
- Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F. Dantrolene - a review of its pharmacology, therapeutic use and new developments. Anaesthesia 2004;59:364-73. PMID 15023108.