Dantrolene – A review of its pharmacology, therapeutic use and new developments

Anaesthesia - Tập 59 Số 4 - Trang 364-373 - 2004
T. Krause1, Mark U. Gerbershagen2, M. Fiege1, Ralf Weißhorn1, Frank Wappler3
1Assistant Professor
2Staff Anaesthesiologist
3Professor of Anaesthesiology, Department of Anaesthesiology, University-Hospital Hamburg-Eppendorf, Hamburg, Germany

Tóm tắt

SummaryHuman 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.

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Tài liệu tham khảo

Rosenberg H, 1994, An update on the malignant hyperthermia syndrome, Annals of the Academy of Medicine, Singapore, 23, 84

10.1136/bmj.3.5772.454

10.1097/00000542-197902000-00008

10.1021/jm00317a011

10.1007/BF00501011

Dykes MH, 1975, Evaluation of a muscle relaxant: dantrolene sodium (Dantrium), Journal of the American Medical Association, 231, 862, 10.1001/jama.1975.03240200058032

10.1093/bja/48.4.297

10.1093/bja/47.1.62

10.1097/00000542-197606000-00005

10.1111/j.1365-2044.1977.tb09985.x

10.1097/00000542-197601000-00013

10.1097/00000542-198204000-00005

Ellis KO, 1974, Mechanism of control of skeletal‐muscle contraction by dantrolene sodium, Archives of Physical Medicine and Rehabilitation, 55, 362

10.1097/00000542-198310000-00002

10.1097/00000542-198904000-00013

Leitman PS, 1974, Pharmacology of dantrolene sodium in children, Archives of Physical Medicine and Rehabilitation, 55, 388

10.2165/00003495-198632020-00003

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

10.1016/S0074-7696(08)60145-X

10.1016/S0006-3495(90)82563-7

10.1038/343559a0

10.1152/ajpcell.1994.266.6.C1485

10.1021/jm9805079

10.1152/physrev.1996.76.4.1027

10.1042/bj3260847

10.1074/jbc.270.31.18465

10.1097/00000542-199606000-00013

10.1074/jbc.272.43.26965

10.1021/bi001502s

10.1074/jbc.M205487200

10.1085/jgp.118.4.355

10.1113/jphysiol.1997.sp021969

10.1085/jgp.115.4.467

10.1074/jbc.275.16.11618

10.1002/(SICI)1097-4598(200001)23:1<4::AID-MUS3>3.0.CO;2-D

10.1073/pnas.96.7.4164

10.1093/hmg/10.25.2879

10.1161/01.CIR.103.4.485

10.1161/01.CIR.103.2.196

10.1093/hmg/10.3.189

10.1097/00002826-200207000-00001

10.1126/science.1862346

10.2741/froemmin

10.1046/j.1432-1327.2000.01566.x

10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D

10.1016/S0960-8966(01)00202-4

10.1086/321270

10.1016/S0021-9258(17)42825-0

10.1111/j.1749-6632.1993.tb38051.x

10.1074/jbc.M006104200

10.1042/0264-6021:3410423

10.4049/jimmunol.167.9.4887

10.1016/S0014-5793(01)03312-9

10.1083/jcb.146.3.621

10.1097/00000542-200209002-01199

10.3109/01480548409014171

10.3109/01480548509038647

10.1097/00000542-199205000-00008

10.1016/S0002-9378(88)80147-9

10.1213/00000539-198703000-00013

10.1213/00000539-198603000-00006

10.1213/00000539-198405000-00001

10.1097/00000542-198504000-00028

10.1213/00000539-199003000-00004

10.1097/00000542-200209002-00071

10.1111/j.1440-1681.1991.tb01482.x

10.1097/00000539-199611000-00056

Wappler F, 2002, Leitlinie zur Therapie der malignen Hyperthermie, Anästhesiologie und Intensivmedizin, 43, 50

Gronert GA, 2000, Anesthesia, 1033

10.1007/BF03011484

Wappler F, 2001, Malignant hyperthermia, European Journal of Anaesthesiology, 18, 632, 10.1097/00003643-200110000-00002

10.1093/bja/60.3.279

10.1007/BF03010703

10.1016/S0022-3468(89)80239-8

10.1111/j.1399-6576.1990.tb03140.x

10.1111/j.1399-6576.1991.tb03377.x

10.1007/s00101-002-0314-9

Gurrera RJ, 1999, Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome, American Journal of Psychiatry, 156, 169, 10.1176/ajp.156.2.169

10.1212/WNL.31.2.132

10.1111/j.1399-6576.1989.tb02990.x

10.1007/s001010170017

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

10.1185/03007998409109576

10.1159/000052817

10.1093/ageing/30.suppl_1.13

10.1136/bmj.305.6863.1225-b

10.1111/j.1365-2044.1993.tb07102.x

10.1111/j.1749-6632.1990.tb16917.x

10.1093/bja/88.5.700

10.1093/bja/66.1.138

10.1016/0140-6736(91)92304-K

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

10.1007/BF01711537

10.1016/0140-6736(92)90248-2

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Anaesthesia

Tập 59 Số 4

364-373

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