Repositioning Candidate Details
| Candidate ID: | R0358 |
| Source ID: | DB01219 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Dantrolene |
| Synonyms: | |
| Molecular Formula: | C14H10N4O5 |
| SMILES: | [O-][N+](=O)C1=CC=C(C=C1)C1=CC=C(O1)C=NN1CC(=O)NC1=O |
| Structure: |
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| DrugBank Description: | Chemically, dantrolene is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin. |
| CAS Number: | 7261-97-4 |
| Molecular Weight: | 314.253 |
| DrugBank Indication: | For use, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. Also used preoperatively, and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible. |
| DrugBank Pharmacology: | Dantrolene is classified as a direct-acting skeletal muscle relaxant. It is currently the only specific and effective treatment for malignant hyperthermia. In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, Dantrium dissociates excitation-contraction coupling, probably by interfering with the release of Ca<sup>2+</sup> from the sarcoplasmic reticulum. In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In selected humans, it has been postulated that “triggering agents” (e.g.,general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis. It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. |
| DrugBank MoA: | Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction. |
| Targets: | Ryanodine receptor 1 |
| Inclusion Criteria: |
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