Chemical: Drug
sevoflurane

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency, Japan (PMDA), and Health Canada (Santé Canada) (HCSC). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

See the legend for more information about drug label sources and PGx Levels.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA, HCSC or other Medicine Agencies around the world - please contact feedback.


Annotated Labels

  1. FDA Label for sevoflurane and CACNA1S,RYR1
  2. HCSC Label for sevoflurane and CACNA1S,RYR1

last updated 11/06/2015

1. FDA Label for sevoflurane and CACNA1S,RYR1

Actionable PGx

Summary

Sevoflurane is a potent (volatile) inhalational anesthetic used to induce or maintain general anesthesia.

Annotation

The FDA-approved label warns that individuals with a genetic predisposition to malignant hyperthermia, or patients with Duchenne Muscular Dystrophy, are at greater risk of developing malignant hyperthermia, or hyperkaelemia, respectively, if administered sevoflurane.

Specific variants in the RYR1 and CACNA1S genes are associated with risk of malignant hyperthermia in individuals administered potent inhalational anesthetics, including sevoflurane. Although the sevoflurane (ULTANE) drug label does not specifically mention genetic testing, the FDA-approved label for sevoflurane (ULTANE) contraindicates it for individuals with known, or suspected, genetic predisposition to malignant hyperthermia.

Excerpts from the FDA-approved sevoflurane (ULTANE) drug label

CONTRAINDICATIONS
Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to
malignant hyperthermia.

One case of malignant hyperthermia was reported in pre-registration clinical trials.

Use of inhaled anesthetic agents has been associated with rare increases to serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the sevoflurane drug label
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label


last updated 12/08/2015

2. HCSC Label for sevoflurane and CACNA1S,RYR1

Actionable PGx

Summary

Sevoflurane is a potent (volatile) inhalational anesthetic used to induce or maintain general anesthesia.

Annotation

The HCSC product monograph warns that individuals with a genetic predisposition to malignant hyperthermia are at an elevated risk of developing malignant hyperthermia, and that patients with Duchenne's Muscular Dystrophy are at an elevated risk of developing hyperkaelemia if administered sevoflurane, or other potent inhalational anesthetics.

Specific variants in the RYR1 and CACNA1S genes are associated with risk of malignant hyperthermia in individuals administered potent inhalational anesthetics, such as sevoflurane. Although the product monograph for sevoflurane does not specifically mention genetic testing, it states that sevoflurane is contraindicated in individuals with known to have a genetic predisposition to malignant hyperthermia.

Excerpts from the sevoflurane product monograph

In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia.

In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been postmarketing reports of malignant hyperthermia. Some of these reports have been fatal.

Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable.

For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the sevoflurane product monograph

Genes and/or phenotypes found in this label


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for sevoflurane

Gene ? Variant?
(144)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
rs111888148 11214321G>A, 1589G>A, 26764G>A, 38946103G>A, Arg530His
G > A
Missense
Arg530His
rs112563513 11258081G>A, 38989863G>A, 7007G>A, 70524G>A, Arg2336His
G > A
Missense
Arg2336His
rs118192116 11210708C>G, 1209C>G, 23151C>G, 38942490C>G, Ile403Met
C > G
Missense
Ile403Met
rs118192122 11259501G>A, 38991283G>A, 71944G>A, 7361G>A, Arg2454His
G > A
Missense
Arg2454His
No VIP available CA No Variant Annotations available
rs118192124 11259494C>T, 38991276C>T, 71937C>T, 7354C>T, Arg2452Trp
C > T
Missense
Arg2452Trp
rs118192161 11203069C>T, 15512C>T, 38934851C>T, 487C>T, Arg163Cys
C > T
Missense
Arg163Cys
rs118192162 11214217A>C, 11214217A>G, 1565A>C, 1565A>G, 26660A>C, 26660A>G, 38945999A>C, 38945999A>G, Tyr522Cys, Tyr522Ser
A > C
A > G
Missense
Tyr522Cys
Tyr522Ser
rs118192163 11253423G>A, 11253423G>C, 38985205G>A, 38985205G>C, 6488G>A, 6488G>C, 65866G>A, 65866G>C, Arg2163His, Arg2163Pro
G > A
G > C
Missense
Arg2163Pro
Arg2163His
rs118192167 11338862A>G, 14372A>G, 14387A>G, 151305A>G, 39070644A>G, Tyr4791Cys, Tyr4796Cys
A > G
Missense
Tyr4796Cys
rs118192170 11343847T>C, 14678T>C, 14693T>C, 156290T>C, 39075629T>C, Ile4893Thr, Ile4898Thr
T > C
Missense
Ile4898Thr
rs118192172 11216403C>T, 1840C>T, 28846C>T, 38948185C>T, Arg614Cys
C > T
Missense
Arg614Cys
rs118192175 11253422C>T, 38985204C>T, 6487C>T, 65865C>T, Arg2163Cys
C > T
Missense
Arg2163Cys
rs118192176 11253437G>A, 38985219G>A, 6502G>A, 65880G>A, Val2168Met
G > A
Missense
Val2168Met
rs118192177 11255141C>G, 11255141C>T, 38986923C>G, 38986923C>T, 6617C>G, 6617C>T, 67584C>G, 67584C>T, Thr2206Arg, Thr2206Met
C > G
C > T
Missense
Thr2206Arg
Thr2206Met
rs118192178 11259756C>G, 11259756C>T, 38991538C>G, 38991538C>T, 72199C>G, 72199C>T, 7522C>G, 7522C>T, Arg2508Cys, Arg2508Gly
C > G
C > T
Missense
Arg2508Cys
Arg2508Gly
rs121918592 1021G>A, 1021G>C, 11207570G>A, 11207570G>C, 20013G>A, 20013G>C, 38939352G>A, 38939352G>C, Gly341Arg
G > A
G > C
Missense
Gly341Arg
rs121918593 11258851G>A, 38990633G>A, 71294G>A, 7300G>A, Gly2434Arg
G > A
Missense
Gly2434Arg
rs121918594 11259513G>A, 38991295G>A, 71956G>A, 7373G>A, Arg2458His
G > A
Missense
Arg2458His
rs121918595 11338952C>T, 14462C>T, 14477C>T, 151395C>T, 39070734C>T, Thr4821Ile, Thr4826Ile
C > T
Missense
Thr4826Ile
No VIP available CA No Variant Annotations available
rs1800559 201029943C>T, 3257G>A, 52518585C>T, 56752G>A, Arg1086His
C > T
Missense
Arg1086His
rs1801086 11205568G>A, 11205568G>C, 11205568G>M, 18011G>A, 18011G>C, 18011G>M, 38937350G>A, 38937350G>C, 38937350G>M, 742G>A, 742G>C, 742G>M, Gly248Arg, RYR1:ARG248GLY
G > A
G > C
Missense
Gly248Arg
No VIP available CA No Variant Annotations available
rs193922747 103T>C, 11199660T>C, 12103T>C, 38931442T>C, Cys35Arg
T > C
Missense
Cys35Arg
No VIP available CA No Variant Annotations available
rs193922753 11203070G>T, 15513G>T, 38934852G>T, 488G>T, Arg163Leu
G > T
Missense
Arg163Leu
VIP No Clinical Annotations available No Variant Annotations available
rs193922770 11214386C>T, 1654C>T, 26829C>T, 38946168C>T, Arg552Trp
C > T
Missense
Arg552Trp
rs193922772 11216404G>T, 1841G>T, 28847G>T, 38948186G>T, Arg614Leu
G > A
G > T
Missense
Arg614Leu
rs193922802 11258513G>A, 38990295G>A, 7048G>A, 70956G>A, Ala2350Thr
G > A
Missense
Ala2350Thr
No VIP available CA No Variant Annotations available
rs193922803 11258528C>T, 38990310C>T, 7063C>T, 70971C>T, Arg2355Trp
C > T
Missense
Arg2355Trp
rs193922807 11258589G>C, 38990371G>C, 71032G>C, 7124G>C, Gly2375Ala
G > C
Missense
Gly2375Ala
rs193922809 11258833G>A, 38990615G>A, 71276G>A, 7282G>A, Ala2428Thr
G > A
Missense
Ala2428Thr
rs193922816 11259500C>T, 38991282C>T, 71943C>T, 7360C>T, Arg2454Cys
C > T
Missense
Arg2454Cys
No VIP available CA No Variant Annotations available
rs193922818 11259757G>A, 38991539G>A, 72200G>A, 7523G>A, Arg2508His
G > A
Missense
Arg2508His
rs193922876 11338972C>T, 14482C>T, 14497C>T, 151415C>T, 39070754C>T, His4828Tyr, His4833Tyr
C > T
Missense
His4833Tyr
rs193922878 11339228C>G, 14497C>G, 14512C>G, 151671C>G, 39071010C>G, Leu4833Val, Leu4838Val
C > G
Missense
Leu4838Val
rs28933396 11258855G>A, 11258855G>T, 38990637G>A, 38990637G>T, 71298G>A, 71298G>T, 7304G>A, 7304G>T, Arg2435His, Arg2435Leu, RYR1:ARG2434HIS, RYR1:ARG2435HIS, RYR1:ARG2436HIS, p.R2435H
G > A
G > T
Missense
Arg2435Leu
Arg2435His
rs28933397 11259512C>T, 38991294C>T, 71955C>T, 7372C>T, 7372CT, ARG2458CYS, Arg2458Cys
C > T
Missense
Arg2458Cys
rs63749869 11339298G>A, 14567G>A, 14582G>A, 151741G>A, 39071080G>A, Arg4856His, Arg4861His
G > A
Missense
Arg4861His
No VIP available CA No Variant Annotations available
rs772226819 201061121G>A, 201091993G>A, 25574C>T, 520C>T, Arg174Trp
G > A
Missense
Arg174Trp
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Sevofluran
  • Sevoflurano [INN-Spanish]
  • Sevofluranum [INN-Latin]
Trade Names
  • Sevorane
  • Ultane
Brand Mixture Names

PharmGKB Accession Id

PA451341

Type(s):

Drug

Description

Sevoflurane (2,2,2-trifluoro-1-[trifluoromethyl]ethyl fluoromethyl ether), also called fluoromethyl, is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. Wikipedia

Source: Drug Bank

Indication

Used for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Sevoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Sevoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase and also binds to the GABA receptor, the large conductance Ca 2+ activated potassium channel, the glutamate receptor, and the glycine receptor.

Source: Drug Bank

Pharmacology

Sevoflurane (also called fluoromethyl) is a halogenated ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. It is often administered in nitrous oxide and pure oxygen. After desflurane it is the volatile anesthetic with the fastest onset and offset. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Relatively little biotransformation, only 5% is metabolized by cytochrome P450 CYP2E1 to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. No other metabolic pathways have been identified for sevoflurane.

Source: Drug Bank

Absorption

Rapidly absorbed into circulation via the lungs, however solubility in the blood is low.

Source: Drug Bank

Half-Life

15-23 hours

Source: Drug Bank

Toxicity

LC 50=49881 ppm/hr (rat), LD 50=10.8 g/kg (rat)

Source: Drug Bank

Route of Elimination

The low solubility of sevoflurane facilitates rapid elimination via the lungs. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized. Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride.

Source: Drug Bank

Chemical Properties

Chemical Formula

C4H3F7O

Source: Drug Bank

Isomeric SMILES

C(OC(C(F)(F)F)C(F)(F)F)F

Source: OpenEye

Canonical SMILES

FCOC(C(F)(F)F)C(F)(F)F

Source: Drug Bank

Average Molecular Weight

200.0548

Source: Drug Bank

Monoisotopic Molecular Weight

200.007212153

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ATP2C1 (source: Drug Bank)
ATP5D (source: Drug Bank)
GABRA1 (source: Drug Bank)
GLRA1 (source: Drug Bank)
GRIA1 (source: Drug Bank)
KCNA1 (source: Drug Bank)
MT-ND1 (source: Drug Bank)
No related drugs are available.

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

Induces
Contraindicated With

Publications related to sevoflurane: 91

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB Summary: very important pharmacogene information for RYR1. Pharmacogenetics and genomics. 2015. Alvarellos Maria L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. British journal of anaesthesia. 2015. Hopkins P M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1-related myopathies: a wide spectrum of phenotypes throughout life. European journal of neurology. 2015. Snoeck M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia, a Scandinavian update. Acta anaesthesiologica Scandinavica. 2015. Broman M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Next-generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness. Anesthesiology. 2015. Fiszer Dorota, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy. Neuromuscular disorders : NMD. 2015. Kraeva N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families. Anaesthesia and intensive care. 2015. Gillies R L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1-related malignant hyperthermia with marked cerebellar involvement - a paradigm of heat-induced CNS injury?. Neuromuscular disorders : NMD. 2015. Forrest Katharine M L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in a 3-year-old child with microstomia. The Journal of craniofacial surgery. 2015. Evans Tyler A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Malignant hyperthermia: a review. Orphanet journal of rare diseases. 2015. Rosenberg Henry, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Functional characterisation of the R2452W ryanodine receptor variant associated with malignant hyperthermia susceptibility. Cell calcium. 2014. Roesl Cornelia, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Next-generation DNA sequencing of a Swedish malignant hyperthermia cohort. Clinical genetics. 2014. Broman M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Improving awareness of nonanesthesia-related malignant hyperthermia presentations: a tale of two brothers. A & A case reports. 2014. Potts Lauren E, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Functional characterization of 2 known ryanodine receptor mutations causing malignant hyperthermia. Anesthesia and analgesia. 2014. Schiemann Anja H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. Orphanet journal of rare diseases. 2014. Klingler Werner, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Using exome data to identify malignant hyperthermia susceptibility mutations. Anesthesiology. 2013. Gonsalves Stephen G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. Neuromuscular disorders : NMD. 2013. Dlamini N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. Anesthesia and analgesia. 2013. Brandom Barbara W, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Nonspecific sarcolemmal cation channels are critical for the pathogenesis of malignant hyperthermia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2013. Eltit José M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Novel double and single ryanodine receptor 1 variants in two Austrian malignant hyperthermia families. Anesthesia and analgesia. 2012. Kaufmann Alexius, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A study of a family with the skeletal muscle RYR1 mutation (c.7354C>T) associated with central core myopathy and malignant hyperthermia susceptibility. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2012. Taylor A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population. Canadian journal of anaesthesia = Journal canadien d'anesthésie. 2011. Kraeva Natasha, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families. Clinical genetics. 2011. Tammaro A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1-related central core myopathy in a Chinese adolescent boy. Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine. 2011. Chan B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Increasing the number of diagnostic mutations in malignant hyperthermia. Human mutation. 2009. Levano Soledad, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphic drug metabolism in anaesthesia. Current drug metabolism. 2009. Restrepo Juan G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A fulminant malignant hyperthermia episode in a patient with ryanodine receptor gene mutation p.Tyr522Ser. Anesthesia and analgesia. 2008. Girard Thierry, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mild clinical and histopathological features in patients who carry the frequent and causative malignant hyperthermia RyR1 mutation p.Thr2206Met. Clinical neuropathology. 2009. Rueffert H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Functional analysis of ryanodine receptor type 1 p.R2508C mutation in exon 47. Journal of anesthesia. 2009. Migita Takako, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Malignant hyperthermia: a pharmacogenetic disorder. Pharmacogenomics. 2008. Stowell Kathryn M. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A double mutation of the ryanodine receptor type 1 gene in a malignant hyperthermia family with multiminicore myopathy. Journal of clinical neurology (Seoul, Korea). 2008. Jeong Seul-Ki, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification of genetic mutations in Australian malignant hyperthermia families using sequencing of RYR1 hotspots. Anaesthesia and intensive care. 2008. Gillies R L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Molecular genetic testing to diagnose malignant hyperthermia susceptibility. Journal of clinical anesthesia. 2008. Girard Thierry, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association between GSTP1 gene polymorphism and serum alpha-GST concentrations undergoing sevoflurane anaesthesia. European journal of anaesthesiology. 2008. Kaymak C, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification and biochemical characterization of a novel ryanodine receptor gene mutation associated with malignant hyperthermia. Anesthesiology. 2008. Anderson Ayuk A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia susceptibility diagnosed with a family-specific ryanodine receptor gene type 1 mutation. Journal of anesthesia. 2008. Tanabe Takahiro, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Central core disease due to recessive mutations in RYR1 gene: is it more common than described?. Muscle & nerve. 2007. Kossugue Patrícia M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia and central core disease causative mutations in Swedish patients. Acta anaesthesiologica Scandinavica. 2007. Broman M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Molecular genetic detection of susceptibility to malignant hyperthermia in Belgian families. Acta anaesthesiologica Belgica. 2007. Heytens L. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. Anesthesiology. 2006. Yang Tianzhong, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutations in RYR1 in malignant hyperthermia and central core disease. Human mutation. 2006. Robinson Rachel, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia. Human mutation. 2006. Galli Lucia, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in Japan: mutation screening of the entire ryanodine receptor type 1 gene coding region by direct sequencing. Anesthesiology. 2006. Ibarra M Carlos A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Perinatal diagnosis of malignant hyperthermia susceptibility. Anesthesiology. 2006. Girard Thierry, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Central core disease is due to RYR1 mutations in more than 90% of patients. Brain : a journal of neurology. 2006. Wu Shiwen, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006. Chelu Mihail G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. Human mutation. 2005. Monnier Nicole, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population. Anesthesiology. 2005. Sambuughin Nyamkhishig, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene. Anesthesiology. 2004. Sei Yoshitatsu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Spontaneous occurrence of the disposition to malignant hyperthermia. Anesthesiology. 2004. Rueffert Henrik, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Screening for mutations in the RYR1 gene in families with malignant hyperthermia. Journal of molecular neuroscience : MN. 2003. Muniz Viviane P, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Patients with malignant hyperthermia demonstrate an altered calcium control mechanism in B lymphocytes. Anesthesiology. 2002. Sei Yoshitatsu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility. Anesthesiology. 2002. Monnier Nicole, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
[Current aspects of the diagnosis of malignant hyperthermia]. Der Anaesthesist. 2002. Rüffert H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Evidence for a spontaneous C1840-T mutation in the RYR1 gene after DNA fingerprinting in a malignant hyperthermia susceptible family. Naunyn-Schmiedeberg's archives of pharmacology. 2002. Steinfath Markus, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region. Cell calcium. 2002. Galli L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. Anesthesiology. 2002. Fiege Marko, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation. Clinical genetics. 2002. Wehner M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Human mutation. 2002. Robinson Rachel L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations. Acta anaesthesiologica Scandinavica. 2002. Rueffert Henrik, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Novel mutations in C-terminal channel region of the ryanodine receptor in malignant hyperthermia patients. Japanese journal of pharmacology. 2002. Oyamada Hideto, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotype-phenotype comparison of the Swiss malignant hyperthermia population. Human mutation. 2001. Girard T, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations. Anesthesiology. 2001. Sambuughin N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families. Neuromuscular disorders : NMD. 2001. Sambuughin N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Homozygous and heterozygous Arg614Cys mutations (1840C-->T) in the ryanodine receptor gene co-segregate with malignant hyperthermia susceptibility in a German family. British journal of anaesthesia. 2001. Rueffert H, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Determination of a positive malignant hyperthermia (MH) disposition without the in vitro contracture test in families carrying the RYR1 Arg614Cys mutation. Clinical genetics. 2001. Rueffert H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Malignant hyperthermia and apparent heat stroke. JAMA. 2001. Tobin J R, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification of the Arg1086His mutation in the alpha subunit of the voltage-dependent calcium channel (CACNA1S) in a North American family with malignant hyperthermia. Clinical genetics. 2001. Stewart S L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor. Human molecular genetics. 2000. Monnier N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree. Human molecular genetics. 2000. Brown R L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in infancy and identification of novel RYR1 mutation. British journal of anaesthesia. 2000. Chamley D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
[Preliminary report: first identification of known mutation in the ryanodine receptor gene in a Japanese malignant hyperthermia pedigree]. Masui. The Japanese journal of anesthesiology. 2000. Ichihara Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Novel mutation in the RYR1 gene (R2454C) in a patient with malignant hyperthermia. Human mutation. 2000. Gencik M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test. Human molecular genetics. 1999. Brandt A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease. Proceedings of the National Academy of Sciences of the United States of America. 1999. Lynch P J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families. Journal of medical genetics. 1999. Barone V, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation. American journal of human genetics. 1998. Manning B M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. The Journal of biological chemistry. 1997. Tong J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia. British journal of anaesthesia. 1997. Quane K A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. American journal of human genetics. 1997. Monnier N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification of heterozygous and homozygous individuals with the novel RYR1 mutation Cys35Arg in a large kindred. Anesthesiology. 1997. Lynch P J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR mutation G1021A (Gly341Arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility. Clinical genetics. 1996. Fagerlund T, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Comparison of the segregation of the RYR1 C1840T mutation with segregation of the caffeine/halothane contracture test results for malignant hyperthermia susceptibility in a large Manitoba Mennonite family. Anesthesiology. 1996. Serfas K D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia. Clinical genetics. 1995. Fagerlund T H, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Ryanodine receptor gene point mutation and malignant hyperthermia susceptibility. Journal of neurology. 1995. Moroni I, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia. Clinical genetics. 1994. Fagerlund T, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A mutation in the human ryanodine receptor gene associated with central core disease. Nature genetics. 1993. Zhang Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nature genetics. 1993. Quane K A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia. Genomics. 1992. Gillard E F, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics. 1991. Gillard E F, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0074-4456-04
DrugBank:
DB01236
ChEBI:
9130
KEGG Compound:
C07520
KEGG Drug:
D00547
PubChem Compound:
5206
PubChem Substance:
46508591
9723
Drugs Product Database (DPD):
2172763
ChemSpider:
5017
Therapeutic Targets Database:
DAP000694
FDA Drug Label at DailyMed:
4c6e76bc-c964-4955-e0a3-511d3386a9cc

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