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| Clinical data | |
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| Trade names | Dantrium, Revonto, Ryanodex |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682576 |
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| Routes of administration | By mouth,intravenous |
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| Pharmacokinetic data | |
| Bioavailability | 70% |
| Metabolism | Liver |
| Excretion | Bile duct,kidney |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.027.895 |
| Chemical and physical data | |
| Formula | C14H10N4O5 |
| Molar mass | 314.257 g·mol−1 |
| 3D model (JSmol) | |
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Dantrolene sodium, sold under the brand nameDantrium among others, is a postsynapticmuscle relaxant that lessensexcitation-contraction coupling inmuscle cells.[5][6][7] It achieves this by inhibitingCa2+ ions release fromsarcoplasmic reticulum stores by antagonizingryanodine receptors.[8] It is the primary drug used for the treatment and prevention ofmalignant hyperthermia, a rare, life-threatening disorder triggered bygeneral anesthesia ordrugs. It is also used in the management ofneuroleptic malignant syndrome, musclespasticity (e.g. afterstrokes, inparaplegia,cerebral palsy, or patients withmultiple sclerosis), and poisoning by2,4-dinitrophenol[9][10] or by the related compoundsdinoseb anddinoterb.[11]
The most frequently occurring side effects include drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhea.[5][6]
It is marketed by Par Pharmaceuticals LLC as Dantrium (in North America) and by Norgine BV as Dantrium, Dantamacrin, or Dantrolen (in Europe). A hospital is recommended to keep a minimum stock of 36 dantrolene vials totaling 720 mg, sufficient for a 70-kg person.[12]
Oral dantrolene is contraindicated for[13]
There are no contraindications for intravenous dantrolene used for prophylaxis or management ofmalignant hyperthermia.[14]
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.[11]
Dantrolene may interact with the following drugs:[15]
Dantrolene depressesexcitation-contraction coupling inskeletal muscle by acting as areceptor antagonist to theryanodine receptor, and decreasing freeintracellularcalcium concentration.[11]
Chemically it is ahydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such asphenytoin.[11]
The poor watersolubility of dantrolene leads to certain difficulties in its use.[11][16] A more water-solubleanalog of dantrolene,azumolene, is under development for similar indications.[16] Azumolene has abromine residue instead of thenitro group found in dantrolene, and is 30 times more water-soluble.[11]
The original patent synthesis started withpara-nitroaniline which undergoesdiazotization followed by acopper(II) chloride catalyzed arylation withfurfural (essentially a modifiedMeerwein arylation). This then reacts with 1-aminohydantoin to form the final product.
Dantrolene was first described in the scientific literature in 1967, as one of severalhydantoin derivatives proposed as a new class of muscle relaxant.[17] Dantrolene underwent extensive further development, and its action onskeletal muscle was described in detail in 1973.[18]
Dantrolene was widely used in the management ofspasticity[19] before its efficacy in treating malignant hyperthermia was discovered by South African anesthesiologist Gaisford Harrison and reported in a landmark 1975 article published in theBritish Journal of Anaesthesia.[20] Harrison experimentally induced malignant hyperthermia withhalothane anesthesia in genetically susceptiblepigs, and obtained an 87.5% survival rate, where seven of his eight experiments survived afterintravenous administration of dantrolene. The efficacy of dantrolene in humans was later confirmed in a large, multicenter study published in 1982,[21] and confirmed epidemiologically in 1993.[22] Before dantrolene, the only available treatment for malignant hyperthermia wasprocaine, which was associated with a 60% mortality rate in animal models.[20]
In March 2024, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Agilus, intended for the treatment of malignant hyperthermia in combination with adequate support measures.[4][23] The applicant for this medicinal product is Norgine B.V.[4] In the formulation of Agilus, the mannitol and sodium hydroxide have been replaced with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and Macrogol 3350 to shorten the preparation time and improve the ease of use.[4] It was designated an orphan drug.[4][24] Dantrolene sodium, hemiheptahydrate (Agilus) was approved for medical use in the European Union in May 2024.[4]
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