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Drug-Target Interaction

Drug

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PubChem ID:15387
Structure:
Synonyms:
1-(4-fluorophenyl)-4-(4-methylpiperidin-1-yl)butan-1-one
1622-79-3
1622-79-3 (hydrochloride)
3575-80-2
4'-fluor-4-(4-methylpiperidino)-butyrophenone
4'-Fluor-4-(4-methylpiperidino)butyrophenon
4'-Fluoro-4-(4-methylpiperidino)butyrophenone
AC1L25SI
AC1Q4NIX
Bunil
Bunil (TN)
Buronil
C16H22FNO
CHEMBL1531134
D07309
L000772
LS-174559
melperon
melperon FG 5111
Melperona
Melperona [INN-Spanish]
MELPERONE
Melperone (INN)
Melperone [BAN:DCF:INN]
Melperone [INN:BAN:DCF]
Melperonum
Melperonum [INN-Latin]
methylperon
Methylperone
Metylperon
Metylperonum
NCGC00167744-01
PDSP1_000849
PDSP2_000836
UNII-J8WA3K39B7
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:

12649767
Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine.. M Grözinger; A Dragicevic; C Hiemke; M Shams; M J Müller; S Härtter (2003) Pharmacopsychiatry display abstract
INTRODUCTION: Melperone, a butyrophenone neuroleptic, is frequently used for its sleep-inducing properties. Despite its common use for more than 30 years, it is not yet characterized regarding its effects on cytochrome P450 s (CYPs). In an open pilot study, effects of melperone on the steady-state blood levels of venlafaxine, a recently introduced serotonin- and noradrenaline reuptake inhibiting antidepressant, were assessed. METHODS: The dose-corrected serum concentrations of venlafaxine and O-desmethylvenlafaxine were analyzed retrospectively in a therapeutic drug-monitoring (TDM) database comprising 94 patients. In addition, three patients received venlafaxine and melperone concomitantly and the serum concentrations of venlafaxine and O-desmethylvenlafaxine were analyzed before, during, and after melperone co-medication. The effect of melperone on CYP2D6 was further assessed in seven patients by means of the dextromethorphan O-demethylation, which serves as a CYP2D6 probe reaction. RESULTS: Patients treated concomitantly with venlafaxine and melperone had significantly higher (mean +/- SD) venlafaxine (3.27 +/- 2.9 vs. 0.97 +/- 0.99 ng/ml per mg/d; p < 0.05) and lower O-desmethylvenlafaxine serum concentrations (0.69 +/- 0.35 vs. 1.51 +/- 0.9 ng/ml per mg/d; p < 0.01) compared to patients without melperone comedication. In the three patients, venlafaxine serum concentrations increased, on average by 52 % during melperone co-medication, whereas O-desmethylvenlafaxine was decreased, on average by 29 %. Administration of melperone over three days elevated the ratio of dextromethorphan to dextrorphan from 0.044 +/- 0.04 to 0.09 +/- 0.083 (p < 0.05). DISCUSSION: This study pointed to an inhibitory effect of melperone on the O-demethylation of venlafaxine. Because the O-demethylation of venlafaxine is almost exclusively catalyzed by CYP2D6 it is concluded that melperone is an inhibitor of CYP2D6. The hypothesis was further corroborated by the inhibitory effect of melperone on the dextromethorphan O-demethylation.