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5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients.
Naunyn Schmiedebergs Arch Pharmacol. 1999 Oct; 360(4):376-81.NS

Abstract

Administration of 5-HT2 receptor agonists induced malignant hyperthermia (MH) in susceptible pigs. Furthermore, the 5-HT2 receptor antagonist ritanserin prevented 5-HT-induced porcine MH. It has been shown that 5-HT2 receptor agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients. The purpose of this study was to investigate the effects of ritanserin on halothane-induced contractures in muscle specimens from MHS patients. Twenty-five patients aged 8-56 years (29.5+/-13.6) classified as MHS by the in vitro contracture test (IVCT) with halothane and caffeine according to the protocol of the European MH Group participated in this study. Muscle specimens were pretreated with ritanserin 10 micromol/l (n= 14), 20 micromol/l (n=14) and 100 micromol/l (n=12) for 10 min and subsequently halothane was added incrementally (0.11-0.22-0.44 mmol/l) to the tissue bath as described in the European MH protocol. The results of the halothane contracture test were used as control. Following administration of halothane, muscle contractures reached a maximum of 16.9+/-4.2 mN. Ritanserin led to a significant inhibition of halothane-induced contractures in MHS muscles. Following pretreatment with ritanserin, halothane-induced contracture maximum was significantly smaller with 7.5+/-3.1 mN after 10 micromol/l ritanserin, 4.9+/-1.5 mN after 20 micromol/l ritanserin and 0.5+/- 0.2 mN after 100 micromol/l ritanserin than without pretreatment. Administration of ritanserin induced at all concentrations a decrease in muscle twitch height. Increase in muscle twitch following halothane was reduced in a concentration-dependent manner by ritanserin. The presented findings indicate that 5-HT might be involved in the mechanisms of halothane-induced MH in humans. Further studies have to determine the pathophysiological role of the 5-HT system in MH, and whether ritanserin could be an alternative for treatment or prevention of halothane-induced MH.

Authors+Show Affiliations

Department of Anaesthesiology, University Hospital Eppendorf, Hamburg, Germany. wappler@uke.uni-hamburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10551274

Citation

Wappler, F, et al. "5-HT2 Receptor Antagonist-mediated Inhibition of Halothane-induced Contractures in Skeletal Muscle Specimens From Malignant Hyperthermia Susceptible Patients." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 360, no. 4, 1999, pp. 376-81.
Wappler F, Scholz J, Fiege M, et al. 5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients. Naunyn Schmiedebergs Arch Pharmacol. 1999;360(4):376-81.
Wappler, F., Scholz, J., Fiege, M., Richter, A., Steinfath, M., Weisshorn, R., & Schulte am Esch, J. (1999). 5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients. Naunyn-Schmiedeberg's Archives of Pharmacology, 360(4), 376-81.
Wappler F, et al. 5-HT2 Receptor Antagonist-mediated Inhibition of Halothane-induced Contractures in Skeletal Muscle Specimens From Malignant Hyperthermia Susceptible Patients. Naunyn Schmiedebergs Arch Pharmacol. 1999;360(4):376-81. PubMed PMID: 10551274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients. AU - Wappler,F, AU - Scholz,J, AU - Fiege,M, AU - Richter,A, AU - Steinfath,M, AU - Weisshorn,R, AU - Schulte am Esch,J, PY - 1999/11/7/pubmed PY - 1999/11/7/medline PY - 1999/11/7/entrez SP - 376 EP - 81 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 360 IS - 4 N2 - Administration of 5-HT2 receptor agonists induced malignant hyperthermia (MH) in susceptible pigs. Furthermore, the 5-HT2 receptor antagonist ritanserin prevented 5-HT-induced porcine MH. It has been shown that 5-HT2 receptor agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients. The purpose of this study was to investigate the effects of ritanserin on halothane-induced contractures in muscle specimens from MHS patients. Twenty-five patients aged 8-56 years (29.5+/-13.6) classified as MHS by the in vitro contracture test (IVCT) with halothane and caffeine according to the protocol of the European MH Group participated in this study. Muscle specimens were pretreated with ritanserin 10 micromol/l (n= 14), 20 micromol/l (n=14) and 100 micromol/l (n=12) for 10 min and subsequently halothane was added incrementally (0.11-0.22-0.44 mmol/l) to the tissue bath as described in the European MH protocol. The results of the halothane contracture test were used as control. Following administration of halothane, muscle contractures reached a maximum of 16.9+/-4.2 mN. Ritanserin led to a significant inhibition of halothane-induced contractures in MHS muscles. Following pretreatment with ritanserin, halothane-induced contracture maximum was significantly smaller with 7.5+/-3.1 mN after 10 micromol/l ritanserin, 4.9+/-1.5 mN after 20 micromol/l ritanserin and 0.5+/- 0.2 mN after 100 micromol/l ritanserin than without pretreatment. Administration of ritanserin induced at all concentrations a decrease in muscle twitch height. Increase in muscle twitch following halothane was reduced in a concentration-dependent manner by ritanserin. The presented findings indicate that 5-HT might be involved in the mechanisms of halothane-induced MH in humans. Further studies have to determine the pathophysiological role of the 5-HT system in MH, and whether ritanserin could be an alternative for treatment or prevention of halothane-induced MH. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/10551274/5_HT2_receptor_antagonist_mediated_inhibition_of_halothane_induced_contractures_in_skeletal_muscle_specimens_from_malignant_hyperthermia_susceptible_patients_ L2 - https://dx.doi.org/10.1007/s002109900062 DB - PRIME DP - Unbound Medicine ER -