Dantrolene

Structural formula
General
Non-proprietary name	Dantrolene
other names	1- [5- (4-nitrophenyl) furfurylideneamino] hydantoin 1 - [{5- (4-Nitrophenyl) furan-2-yl} methylideneamino] imidazolidine-2,4-dione ( IUPAC ) Dantrolenum ( Latin )
Molecular formula	C 14 H 10 N 4 O 5
Brief description	orange powder
External identifiers / databases
CAS number 7261-97-4 14663-23-1 ( sodium salt ) EC number 230-684-8 ECHA InfoCard 100,027,895 PubChem 6914273 ChemSpider 5290202 DrugBank DB01219 Wikidata Q421274
Drug information
ATC code	M03 CA01
Drug class	Muscle relaxant
properties
Molar mass	314.25 g · mol -1
Physical state	firmly
Melting point	279-280 ° C
pK s value	7.5
solubility	little in water (146 mg l −1 at 25 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Sodium salt no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
Toxicological data	> 7000 mg kg −1 ( LD 50 ,  mouse ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Dantrolene is a hydantoin - derivative from the group of muscle relaxants and as a drug , orally in capsule form for treating spastic syndromes with pathologically increased muscle tension and intravenously in the malignant hyperthermia and when neuroleptic malignant syndrome used. The drug is manufactured by the Norgine company in Wettenberg .

Dantrolene, synthesized by Snyder and his colleagues in 1967 and proposed by Gaisford Harrison for the treatment of malignant hyperthermia, was introduced into clinical practice in 1979.

Clinical information

Dantrolene inhibits the release of calcium ions (Ca ²⁺ ) from the sarcoplasmic reticulum (without influencing the Ca ²⁺ reuptake) probably by inhibiting the ryanodine receptor and can thus break the uncontrolled contractions of the entire skeletal muscles. Malignant hyperthermia is a rare but life-threatening complication of anesthesia. Trigger substances are volatile inhalation anesthetics and depolarizing muscle relaxants such as suxamethonium . A predisposing cause for the disease is often a mutation in the RYR1 gene coding for a ryanodine receptor . A sufficient supply of dantrolene for emergency therapy is essential in operating clinics and also in anesthesiological practices that treat patients under general anesthesia on an outpatient basis.

Another possible application is the treatment of neuroleptic malignant syndrome . There are indications that dantrolene could also be helpful in the treatment of hyperthermia, which often occurs in the case of intoxication with MDMA (ecstasy).

One injection bottle contains 20 mg dantrolene sodium and 3 g mannitol as dry substance (powder). To prepare an infusion solution, the contents of a bottle are dissolved with 60 ml of water for injections (to avoid the drawing up of undissolved dantrolene crystals - with the risk of reactions at the injection site from reddening to tissue necrosis - a filtration device (filter needle or filter needle) may be required . Filter cannula) can be used). The pH is then 9.5. For the treatment of malignant hyperthermia in adults, 2.5 to 10 mg / kg and more, about 200 mg (10 injection bottles) to 800 mg, are required.

unwanted effects

Since dantrolene lowers the intracellular calcium ion concentration even at rest and thus has a low muscle relaxant effect, breathing weakness that requires monitoring can occur during the clinical duration of action of 5 to 8 hours after use. In the case of a longer treatment duration, the alkaline dantrolene should be administered via a central venous catheter, as necrosis may occur if it is accidentally injected into the tissue. Other side effects can include nausea, vomiting, headache, dizziness, diarrhea and allergic reactions. Dantrolene has also been causally linked to pleural effusion .

Trade names

Monopreparations : Dantamacrine (D, CH), Dantrolen i. v. (D, CH)

Web links

Commons : Dantrolene  - Collection of images, videos and audio files

• Beverley A. Britt: Dantrolene . In: Canadian Anesthetists' Society Journal . tape 31 , no. 1 , 1984, p. 61 , doi : 10.1007 / BF03011484 .

Individual evidence

1. ↑ ^{a b} entry on dantrolene. In: Römpp Online . Georg Thieme Verlag, accessed on November 12, 2014.
2. ↑ ^{a b c} Entry on dantrolene in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ↑ Dantrolene sodium salt data sheet from Sigma-Aldrich , accessed on May 25, 2011 ( PDF ).
4. ↑ HR Snyder Jr., CS Davis, RK Bickerton, RP Halliday: 1- [(5-Arylfurfurylidine)] amino hydantoins. A new class of muscle relaxants. In: J Med Chem. Volume 10, 1967, pp. 807-810.
5. ↑ Michael Heck, Michael Fresenius: Repetitorium Anaesthesiologie. Preparation for the anesthesiological specialist examination and the European diploma in anesthesiology. 3rd, completely revised edition. Springer, Berlin / Heidelberg / New York et al. 2001, ISBN 3-540-67331-8 , p. 804.
6. ↑ German Society for Anesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine: S1 guideline: Therapy of malignant hyperthermia. Developed by Werner Klingler, Norbert Roewer, Frank Schuster and Frank Wappler. In: Anästh Intensivmed. Volume 59, 2018, pp. 204–208, here: p. 207.
7. ^ Krause et al .: Dantrolene - A review of its pharmacology, therapeutic use and new developments. Anaesthesia, 2004, Vol. 59, pp. 364-373, PMID 15023108 (review article).
8. ^ Hall & Henry: Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br. J. Anaesth, 2006, Vol. 96, pp. 678-685, PMID 16595612 .
9. ↑ ifap Service Institute for Doctors and Pharmacists GmbH: Filter out dantrolene crystals before administration .
10. ↑ German Society for Anesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine: S1 guideline: Therapy of malignant hyperthermia. Developed by Werner Klingler, Norbert Roewer, Frank Schuster and Frank Wappler. In: Anästh Intensivmed. Volume 59, 2018, pp. 204–208, here: p. 205.
11. ^ S1 guideline: Therapy of malignant hyperthermia. 2018, p. 207.
12. ↑ Berthold Jany, Tobias Welte: Pleural effusion in adults - causes, diagnosis and therapy. In: Deutsches Ärzteblatt. Volume 116, No. 21, (May) 2019, pp. 377-385, here: p. 380.

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