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Drug-Target Interaction

Drug

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PubChem ID:38945
Structure:
Synonyms:
(-)-2-Amino-N-(2,6-dimethylphenyl)propanamide
(S)-Tocainide
2',6'-Propionoxylidide, 2-amino-
2-Amino-2',6'-propionoxylidide
2-AMINO-N-(2,6-DIMETHYLPHENYL)PROPANAMIDE
2-Amino-N-(2,6-dimethylphenyl)propionamid
35891-93-1
35891-93-1 (mono-hydrochloride)
41708-72-9
53984-26-2
53984-75-1
76213-25-7
AB00514717
AC-16017
AC1L20PS
AC1Q5LWE
Alanyl-2,6-xylidide
Ambap41708-72-9
Astra W 36095
BPBio1_001335
BRD-A92670106-003-03-9
BRN 2416564
BSPBio_001213
C07142
C11H16N2O
CCG-100842
CHEBI:9611
CHEMBL1762
CPD000466388
D06172
DB01056
EINECS 255-505-0
HMS2051G06
HMS2232D16
LS-125003
MLS000759525
MLS001423966
N-(2,6-dimethylphenyl)alaninamide
NCGC00162129-01
NCGC00162129-02
NCGC00162129-03
Prestwick0_001027
Prestwick1_001027
Prestwick2_001027
Prestwick3_001027
Propanamide, 2-amino-N-(2,6-dimethylphenyl)-
Propanamide, 2-amino-N-(2,6-dimethylphenyl)-, (-)-
Propanamide, 2-amino-N-(2,6-dimethylphenyl)-, (S)-
SAM001246759
SMR000466388
SPBio_003074
Taquidil
Tocainida
Tocainida [INN-Spanish]
Tocainide
Tocainide (USAN/INN)
Tocainide Hydrochloride
Tocainide [USAN:BAN:INN]
Tocainidum
Tocainidum [INN-Latin]
Tonocard
UNII-27DXO59SAN
W-36095
ATC-Codes:

Target

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Uniprot ID:CP1A2_HUMAN
Synonyms:
CYPIA2
Cytochrome P450 1A2
P(3)450
P450 4
P450-P3
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:2HI4
Structure:
2HI4

Binding Affinities:

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

References:

10215663
Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide.. X Wei; R Dai; S Zhai; K E Thummel; F K Friedman; R E Vestal (1999) The Journal of pharmacology and experimental therapeutics display abstract
Mexiletine, lidocaine, and tocainide are class IB antiarrhythmic drugs that are used for the treatment of ventricular arrhythmias and are known to inhibit drug metabolism. The objectives of this study were to characterize the inhibitory effects of mexiletine, lidocaine, and tocainide on cytochrome P-450 1A2 (CYP1A2) activity in human liver microsomes and to evaluate their relative inhibitory potencies by using a molecular model of this P-450 isozyme. The inhibitory effect of mexiletine, lidocaine, and tocainide on cytochrome CYP1A2 in human liver microsomes was examined with methoxyresorufin O-demethylase activity as an index of the catalytic activity of this P-450 isozyme. The kinetic inhibition types and Ki values were determined by Lineweaver-Burk plots and Dixon plots, respectively. Molecular modeling was used to assess the interaction of these agents with the CYP1A2 active site. Methoxyresorufin O-demethylase activity was inhibited 67 +/- 8%, 20 +/- 5%, and 7 +/- 4% by 2 mM mexiletine, lidocaine, and tocainide, respectively. Mexiletine and lidocaine exhibited competitive inhibition with Ki values of 0.28 +/- 0.12 mM and 1.54 +/- 0.74 mM, respectively, whereas the inhibition type of tocainide could not be determined because of its weak potency. A charge interaction between mexiletine and the Asp313 side chain in the CYP1A2 active site was found, and varying degrees of hydrogen bond formation between these three compounds and the CYP1A2 active site were observed. The in vitro inhibitory potencies in human liver microsomes (mexiletine > lidocaine > tocainide) are consistent with the structural interactions found in a molecular model of the active site of CYP1A2.