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Drug-Target Interaction

Drug

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PubChem ID:3562
Structure:
Synonyms:
(+-)-2-Bromo-2-chloro-1,1,1-trifluoroethane
(R)-2-Bromo-2-chloro-1,1,1-trifluoroethane
1,1,1-Trifluoro-2-bromo-2-chloroethane
1,1,1-Trifluoro-2-chloro-2-bromoethane
1-Bromo-1-chloro-2,2,2-trifluoroethane
151-67-7
16730_FLUKA
2,2,2-Trifluoro-1-chloro-1-bromoethane
2-Brom-2-chlor-1,1,1-trifluorethan
2-BROMO-2-CHLORO-1,1,1-TRIFLUOROETHANE
4-01-00-00156 (Beilstein Handbook Reference)
51230-17-2
AC1L1G7T
Alotano
Alotano [DCIT]
Anestan
B4388_SIGMA
BCQZXOMGPXTTIC-UHFFFAOYSA-
BRN 1736947
Bromchlortrifluoraethanum
Bromochlorotrifluoroethane
C07515
C2HBrClF3
CCRIS 6244
Cf3chclbr
Chalothane
CHEBI:5615
CHEMBL931
D00542
D006221
DB01159
DB02330
EINECS 205-796-5
Ethane, 1-bromo-1-chloro-2,2,2-trifluoro-
Ethane, 2-bromo-2-chloro-1,1,1-trifluoro-
Ethane, 2-bromo-2-chloro-1,1,1-trifluoro-, (+-)-
Ethane, 2-bromo-2-chloro-1,1,1-trifluoro-, (R)-
Fluktan
Fluorotane
Fluorothane
Fluothane
Fluothane (TN)
Freon 123B1
Ftorotan
Ftorotan [Russian]
Ftuorotan
Halan
Halotan
Halotano
Halotano [INN-Spanish]
Halothan
Halothane
Halothane (JP15/USP/INN)
Halothane (JP16/USP/INN)
Halothane [Anaesthetics, volatile]
Halothane [BAN:INN:JAN]
Halothane [INN:BAN:JAN]
Halothanum
Halothanum [INN-Latin]
Halsan
HMS2094K17
HSDB 6753
LS-881
Narcotan
Narcotane
Narcotann ne-spofa
Narcotann NE-spofa [Russian]
Narkotan
NCGC00090868-01
NCGC00090868-02
NCGC00090868-03
NSC 143490
NSC143490
Phthorothanum
Rhodialothan
UNII-UQT9G45D1P
WLN: GYEXFFF
ATC-Codes:
Side-Effects:
Side-EffectFrequency
arrhythmia0
cardiac arrest0
hypotension0
nausea0
vomiting0
hepatic necrosis0
respiratory arrest0

Target

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Uniprot ID:CP2D6_HUMAN
Synonyms:
CYPIID6
Cytochrome P450 2D6
Debrisoquine 4-hydroxylase
P450-DB1
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:2F9Q
Structure:
2F9Q

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----

References:

11996015
8886607
Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4.. D K Spracklin; K E Thummel; E D Kharasch (1996) Drug metabolism and disposition: the biological fate of chemicals display abstract
The anesthetic halothane undergoes extensive oxidative and reductive biotransformation, resulting in metabolites that cause hepatotoxicity. Halothane is reduced anaerobically by cytochrome P450 (P450) to the volatile metabolites 2-chloro-1,1-difluoroethene (CDE) and 2-chloro-1,1,1-trifluoroethane (CTE). The purpose of this investigation was to identify the human P450 isoform(s) responsible for reductive halothane metabolism. CDE and CTE formation from halothane metabolism by human liver microsomes was determined by GC/MS analysis. Halothane metabolism to CDE and CTE under reductive conditions was completely inhibited by carbon monoxide, which implicates exclusively P450 in this reaction. Eadie-Hofstee plots of both CDE and CTE formation were nonlinear, suggesting multiple P450 isoform involvement. Microsomal CDE and CTE formation were each inhibited 40-50% by P450 2A6-selective inhibitors (coumarin and 8-methoxypsoralen) and 55-60% by P450 3A4-selective inhibitors (ketoconazole and troleandomycin). P450 1A-, 2B6-, 2C9/10-, and 2D6-selective inhibitors (7,8-benzoflavone, furafylline, orphenadrine, sulfaphenazole, and quinidine) had no significant effect on reductive halothane metabolism. Measurement of product formation catalyzed by a panel of cDNA-expressed P450 isoforms revealed that maximal rates of CDE formation occurred with P450 2A6, followed by P450 3A4. P450 3A4 was the most effective catalyst of CTE formation. Among a panel of 11 different human livers, there were significant linear correlations between the rate of CDE formation and both 2A6 activity (r = 0.64, p < 0.04) and 3A4 activity (r = 0.64, p < 0.03). Similarly, there were significant linear correlations between CTE formation and both 2A6 activity (r = 0.55, p < 0.08) and 3A4 activity (r = 0.77, p < 0.005). The P450 2E1 inhibitors 4-methylpyrazole and diethyldithiocarbamate inhibited CDE and CTE formation by 20-45% and 40-50%, respectively; however, cDNA-expressed P450 2E1 did not catalyze significant amounts of CDE or CTE production, and microsomal metabolite formation was not correlated with P450 2E1 activity. This investigation demonstrated that human liver microsomal reductive halothane metabolism is catalyzed predominantly by P450 2A6 and 3A4. This isoform selectivity for anaerobic halothane metabolism contrasts with that for oxidative human halothane metabolism, which is catalyzed predominantly by P450 2E1.