Dantrolene
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Dantrolene
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| Systematic (IUPAC) name | |
| 1-{[5-(4-nitrophenyl)-2-furyl]methylideneamino} imidazolidine-2,4-dione |
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| Identifiers | |
| CAS number | |
| ATC code | M03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C14H10N4O5 |
| Mol. mass | 314.253 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | 70% |
| Metabolism | Liver |
| Half life | ? |
| Excretion | Biliary, renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral, intravenous |
Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), ecstasy intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning.[1] It is marketed by Procter & Gamble as Dantrium (in North America) and Dantrolen (Europe).
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[edit] Chemistry
Chemically it is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin.[1]
The related substance azumolene is under development for similar indications. It has a bromine residue instead of the nitro group, and is 30 times more water-soluble.[1]
[edit] Mode of action
Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing intracellular calcium concentration.[1]
[edit] Contraindications
Dantrolene cannot be used in people with:[citation needed]
- preexisting liver disease
- compromised lung function
- severe cardiovascular impairment
- known hypersensitivity to dantrolene
- pediatric patients under 5 years of age
- whenever good muscular balance/strength is needed to maintain an upright position, motoric function, or proper neuromuscular balance
If the indication is a medical emergency such as malignant hyperthermia, the only significant contraindication is hypersensitivity.[citation needed]
[edit] Pregnancy and breastfeeding
If needed in pregnancy, adequate human studies are lacking, therefore the drug should be given in pregnant women only if clearly indicated. It may cause hypotonia in the newborn if given closely before delivery.[1]
Dantrolene should not be given to breastfeeding mothers. If a treatment is necessary, breastfeeding should be terminated.[citation needed]
[edit] Side effects
CNS side effects are quite frequently noted and encompass speech and visual disturbances, mental depression and confusion, hallucinations, headache, insomnia and exacerbation or precipitation of seizures, and increased nervousness. Infrequent cases of respiratory depression or a feeling of suffocation have been observed. Dantrolene often causes sedation severe enough to incapacitate the patient to drive or operate machinery.
Gastrointestinal effects include bad taste, anorexia, nausea, vomiting, abdominal cramps, and diarrhea.
Hepatic side effects may be seen either as asymptomatic elevation of liver enzymes and/or bilirubin or, most severe, as fatal and nonfatal hepatitis. The risk of hepatitis is associated with the duration of treatment and the daily dose. In patients treated for hyperthermia, no liver toxicity has been observed so far.
Pleural effusion with pericarditis (oral treatment only), rare cases of bone marrow damage, diffuse myalgias, backache, dermatologic reactions, transient cardiovascular reactions, and crystalluria have additionally been seen. Muscle weakness may persist for several days following treatment.
[edit] Mutagenicity and carcinogenity
Dantrolene gave positive results in animal high dose studies (with and without enzymatic activation) regarding mutagenicity and carcinogenity. No evidence for human mutagenicity and carcinogenity has been found during the long years of clinical experience.[citation needed]
[edit] Drug interactions
Dantrolene may interact with the following drugs:[citation needed]
- Calcium channel blockers of the diltiazem/verapamil type: Intravenous treatment with dantrolene and concomitant calcium channel blocker treatment may lead to severe cardiovascular collapse, arrhythmias, myocardial depressions, and hyperkalemia.
- Vecuronium bromide: Neuromuscular blockade is potentiated.
- CNS depressants: Sedative action is potentiated. Benzodiazepines may also cause additive muscle weakness.
- Estrogens: May enhance liver toxicity of dantrolene in women over 35 years of age.
[edit] References
- ^ a b c d e Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F (2004). "Dantrolene--a review of its pharmacology, therapeutic use and new developments". Anaesthesia 59 (4): 364-73. doi:. PMID 15023108.
[edit] External links
- http://www.kompendium.ch/MonographieTxt.aspx?lang=de&MonType=fi Swiss Drug Compendium on oral Dantrolene (German)
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