[Effects of serotonin 2 receptor agonists on skeletal muscle preparations in patients with a disposition toward malignant hyperthermia].
In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown that serotonin (5-HT2) receptor agonists can induce MH and "psychotic" behaviour. Both can be prevented by 5-HT2 receptor antagonists. Furthermore, free levels of serotonin in plasma increased concomitantly with clinical and laboratory parameters during halothane-induced MH in pigs. In this study the in vitro-effects of the 5-HT2 receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and normal (MHN) patients. METHODS. Muscle biopsies were obtained from 37 patients aged 5-69 years (23.6 +/- 5.3 years) with clinical suspicion for MH. The patients were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the DOI study. DOI was added to the organ bath in a concentration of 0.02 mmol/l. The in vitro effects on contracture development and muscle twitch were observed for 120 min. RESULTS. Muscle specimens of all patients developed contractures after administration of DOI. However, DOI produced an earlier development of contracture in MHS (17.0 +/- 1.8 min; n = 17) than in MHN (64.7 +/- 5.9 min; n = 15) muscles. In MHS muscles, contractures were more distinct than in MHN muscles; at the end of the experiment, contractures had reached a maximum of 12.5 +/- 0.9 mN in MHS and 5.1 +/- 0.7 mN in MHN muscles. Muscle twitch following DOI administration was reduced significantly in both MHS and MHN muscles. The results of four MHE muscles were comparable with MHS. CONCLUSION. The present study supports the assumption that an altered serotonin system might be involved in the development of MH. In further studies it should investigated whether 5-HT2 receptors of skeletal muscles from MHS subjects are disordered in function or structure. 5-HT2 receptor agonists should be considered as MH-triggering agents.
Wappler
F
F
Abteilung für Anästhesiologie, Universitäts-Krankenhaus Eppendorf, Hamburg.
Roewer
N
N
Köchling
A
A
Scholz
J
J
Steinfath
M
M
Rumberger
E
E
Löscher
W
W
Schulte am Esch
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000662:Amphetamines / Q000494:pharmacology*; D002648:Child; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology*; D011446:Prospective Studies; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
Effekte von Serotonin2-Rezeptoragonisten auf Skelett-muskelpräparate von Patienten mit Disposition zu maligner Hyperthermie.