Дантролен натрийы: Қасиеттері, қолданылуы және ескертулер

Chemical compound

Dantrolene sodium, sold under the brand name Dantrium among others, is a postsynaptic muscle relaxant that lessens excitation contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors. It is the primary drug used for the treatment and prevention of malignant hyperthermia, a rare, life threatening disorder triggered by general anesthesia or drugs. 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), and poisoning by 2,4 dinitrophenol or by the related compounds dinoseb and dinoterb.

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. Calcium channel blockers of the diltiazem/verapamil type: Intravenous treatment with dantrolene and concomitant calcium channel blocker treatment may lead to severe cardiovascular collapse, abnormal heart rhythms, myocardial depressions, and high blood potassium. Nondepolarizing neuromuscular blocking agents, such as vecuronium bromide: Neuromuscular blockade is potentiated. CNS depressants: Sedative action is potentiated. Benzodiazepines may also cause additive muscle weakness. Combined oral contraceptives and hormone replacement therapy with estrogens may enhance liver toxicity of dantrolene, particularly in women over 35 years of age.

Dantrolene depresses excitation contraction coupling in skeletal muscle by acting as a receptor antagonist to the ryanodine receptor, and decreasing free intracellular calcium concentration. The poor water solubility of dantrolene leads to certain difficulties in its use. A more water soluble analog of dantrolene, azumolene, is under development for similar indications. Davis and Snyder; (1968 to Norwich Pharma Co).]]

Dantrolene was first described in the scientific literature in 1967, as one of several hydantoin derivatives proposed as a new class of muscle relaxant. Dantrolene was widely used in the management of spasticity before its efficacy in treating malignant hyperthermia was discovered by South African anesthesiologist Gaisford Harrison and reported in a landmark 1975 article published in the British Journal of Anaesthesia. Harrison experimentally induced malignant hyperthermia with halothane anesthesia in genetically susceptible pigs, and obtained an 87.5% survival rate, where seven of his eight experiments survived after intravenous administration of dantrolene. The efficacy of dantrolene in humans was later confirmed in a large, multicenter study published in 1982, and confirmed epidemiologically in 1993. Before dantrolene, the only available treatment for malignant hyperthermia was procaine, which was associated with a 60% mortality rate in animal models. 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.