Document Detail

Effects of the 5-HT2 receptor antagonist ritanserin on halothane-induced increase of inositol phosphates in porcine malignant hyperthermia.
MedLine Citation:
PMID:  8938657     Owner:  NLM     Status:  MEDLINE    
Recent studies have shown a significant increase of inositol phosphates (IPs) in skeletal muscle during episodes of halothane-induced malignant hyperthermia (MH) in pigs. After treatment with dantrolene and disappearance of MH crisis the IP concentrations returned to basal levels. In order to examine if the increase of IPs during halothane-induced MH may be related to an enhanced IP synthesis in response to activation of 5-HT2 (5-hydroxytryptamine) receptors, the effects of ritanserin, a selective 5-HT2 receptor antagonist, on IP levels were investigated. Biopsies of skeletal muscle of the hindlimbs were obtained in random order and IPs were determined in homozygous MH-susceptible (MHS) and MH-non-susceptible (MHN) swine in the following order: (1) basal, (2) after treatment with ritanserin (2.0 mg/kg), (3) after halothane challenge (3 vol% for 20 min). Basal concentrations of all IPs were higher in MHS than in MHN swine. Ritanserin did not cause any significant changes of IP levels compared to the basal concentrations in MHS and MHN pigs. In MHS pigs, ritanserin did not prevent a halothane-induced MH-crisis. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 levels were increased in MHS (during MH crisis) vs. basal concentrations, whereas no changes were found in MHN pigs. Since the increases of IP levels in MHS pigs during MH crisis found in the present study were comparable to those without pretreatment with ritanserin, shown by recent studies, it may be concluded that ritanserin does not prevent the increase of IPs during a halothane-induced MH. Thus, the present data indicate that increases of IP levels during halothane-induced MH in swine are due to other mechanisms than 5-HT mediated enhancement of IP synthesis.
A Richter; J Scholz; W Löscher; P H Tonner; F Wappler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  354     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-03-07     Completed Date:  1997-03-07     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  593-7     Citation Subset:  IM    
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
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MeSH Terms
Anesthetics, Inhalation / adverse effects
Halothane / adverse effects
Inositol 1,4,5-Trisphosphate / metabolism
Inositol Phosphates / metabolism*
Malignant Hyperthermia / etiology*,  metabolism
Muscle, Skeletal / chemistry*
Ritanserin / pharmacology*
Serotonin Antagonists / pharmacology*
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Inositol Phosphates; 0/Serotonin Antagonists; 151-67-7/Halothane; 85166-31-0/Inositol 1,4,5-Trisphosphate; 87051-43-2/Ritanserin

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