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Drug-Target Interaction

Drug

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PubChem ID:30131
Structure:
Synonyms:
( )-(1S,2R)-Ethyl-2-dimethylamino-1-phenyl-3-cyclohexen-1-carboxylat
()-ethyl trans-2-(dimethylamino)-1-phenyl-3-cyclohexene-1-carboxylate
()-trans-tilidine
(+)-Ethyl trans-2-(dimethylamino)-1-phenyl-3-cyclohexene-1-carboxylate
(+/-)-trans-Tilidine
20380-58-9
3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester,
3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, (1R,2S)-rel-
3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, trans-
3-cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, trans-(+)-
3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, trans-(+-)-
32447-90-8
C17H23NO2
DEA No. 9750
Dextilidina [INN-Spanish]
Dextilidine
Dextilidine [INN]
Dextilidinum [INN-Latin]
dl-trans-Tilidine
EINECS 243-774-7
EINECS 251-048-6
EINECS 257-522-9
ethyl (1S,2R)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate
Ethyl trans-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate
Go-1261
LS-173827
LS-57432
Tilidate
Tilidate [BAN]
Tilidina [DCIT]
TILIDINE
Tilidine Hydrochloride ((+-)-trans-tilidine)
Tilidine Hydrochloride, (+-)-211Trans
Tilidine [USAN:INN]
Tilidino [INN-Spanish]
Tilidinum [INN-Latin]
trans-Tilidine
Valerone
Valoron
ATC-Codes:

Target

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Uniprot ID:Q38LG2_HUMAN
Synonyms:
Cytochrome P450 2D6
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

18516595
In vitro metabolism of the opioid tilidine and interaction of tilidine and nortilidine with CYP3A4, CYP2C19, and CYP2D6.. Johanna Weiss; Evelyn Sawa; Klaus-Dieter Riedel; Walter Emil Haefeli; Gerd Mikus (2008) Naunyn-Schmiedeberg's archives of pharmacology display abstract
Tilidine is one of the most widely used narcotics in Germany and Belgium. The compound's active metabolite nortilidine easily penetrates the blood-brain barrier and activates the mu-opioid receptor. Thus far, the enzymes involved in tilidine metabolism are unknown. Therefore, the aim of our study was to identify the cytochrome P450 isozymes (CYPs) involved in N-demethylation of tilidine in vitro. We used human liver microsomes as well as recombinant CYPs to investigate the demethylation of tilidine to nortilidine and quantified nortilidine by liquid chromatography-tandem mass spectrometry. Inhibition of CYPs was quantified with commercial kits. Moreover, inhibition of ABCB1 and ABCG2 was investigated. Our results demonstrated that N-demethylation of tilidine to nortilidine followed a Michaelis-Menten kinetic with a K(m) value of 36 +/- 13 microM and a v(max) value of 85 +/- 18 nmol/mg/h. This metabolic step was inhibited by CYP3A4 and CYP2C19 inhibitors. Investigations with recombinant CYP3A4 and CYP2C19 confirmed that the demethylation of tilidine occurs via these two CYPs. Inhibition assays demonstrated that tilidine and nortilidine can also inhibit CYP3A4, CYP2C19, CYP2D6, ABCB1, but not ABCG2, whereas inhibition of CYP2D6 and possibly also of CYP3A4 might be clinically relevant. By calculating the metabolic clearance based on the in vitro and published in vivo data, CYP3A4 and CYP2C19 were identified as the main elimination routes of tilidine. In vivo, drug-drug interactions of tilidine with CYP3A4 or CYP2C19 inhibitors are to be anticipated, whereas substrates of CYP2C19, ABCB1, or ABCG2 will presumably not be influenced by tilidine or nortilidine.