Dantrolene – A review of its pharmacology, therapeutic use and new developments
Tóm tắt
Human malignant hyperthermia is a life‐threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation–contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene‐binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.
Từ khóa
Tài liệu tham khảo
Rosenberg H, 1994, An update on the malignant hyperthermia syndrome, Annals of the Academy of Medicine, Singapore, 23, 84
Dykes MH, 1975, Evaluation of a muscle relaxant: dantrolene sodium (Dantrium), Journal of the American Medical Association, 231, 862, 10.1001/jama.1975.03240200058032
Ellis KO, 1974, Mechanism of control of skeletal‐muscle contraction by dantrolene sodium, Archives of Physical Medicine and Rehabilitation, 55, 362
Leitman PS, 1974, Pharmacology of dantrolene sodium in children, Archives of Physical Medicine and Rehabilitation, 55, 388
Protasi F, 2002, Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells, Frontiers in Bioscience, 7, 650, 10.2741/A801
Wappler F, 2002, Leitlinie zur Therapie der malignen Hyperthermie, Anästhesiologie und Intensivmedizin, 43, 50
Gronert GA, 2000, Anesthesia, 1033
Wappler F, 2001, Malignant hyperthermia, European Journal of Anaesthesiology, 18, 632, 10.1097/00003643-200110000-00002
Gurrera RJ, 1999, Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome, American Journal of Psychiatry, 156, 169, 10.1176/ajp.156.2.169
Rosenberg MR, 1989, Neuroleptic malignant syndrome. Review of response to therapy, Archives of International Medicine, 149, 1927, 10.1001/archinte.1989.00390090009002
Marelli A, 1996, The neuroleptic malignant syndrome (NMS). A report of a clinical case with a protracted and recurrent course. A review of the literature, Minerva Medica, 87, 45
Köchling A, 1998, Rhabdomyolysis following severe physical exercise in a patient with predisposition to malignant hyperthermia, Anaesthesia and Intensive Care, 26, 315, 10.1177/0310057X9802600317