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Drug-Target Interaction

Drug

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PubChem ID:2519
Structure:
Synonyms:
07E4FB58-FD79-4175-8E3D-05BF96954522
1,3,7-trimethyl-1,3,7-trihydropurine-2,6-dione
1,3,7-trimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
1,3,7-trimethyl-2,6-dioxo-1,2,3,6-tetrahydropurine
1,3,7-Trimethyl-2,6-dioxopurine
1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
1,3,7-trimethylpurine-2,6-dione
1,3,7-Trimethylxanthine
1-3-7-TRIMETHYLXANTHINE
1-methyltheobromine
1gfz
1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-
1l5q
1l7x
27602_FLUKA
2a3b
3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion
3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion (coffein)
3,7-dihydro-1,3,7-trimethyl-1H-purine
3,7-dihydro-1,3,7-trimethyl-1H-purine (9CI)
3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
5-26-13-00558 (Beilstein Handbook Reference)
5-26-13-00558 (Beilstein)
58-08-2
7-Methyltheophylline
71701-02-5
75035_FLUKA
95789-13-2
A.S.A. and Codeine Compound
AC-12774
AC1L1DV2
AC1Q3Z23
ACETAMINOPHEN, ASPIRIN AND CAFFEINE
ACETAMINOPHEN, BUTALBITAL AND CAFFEINE
ACETAMINOPHEN, BUTALBITAL, AND CAFFEINE
ACETAMINOPHEN, BUTALBITAL, CAFFEINE, AND CODEINE PHOSPHATE
ACETAMINOPHEN, CAFFEINE, AND DIHYDROCODEINE BITARTRATE
ACon1_000085
AI3-20154
AIDS-001649
AIDS001649
AKOS000121334
Alert-Pep
Anacin
Anacin Maximum Strength
Anhydrous caffeine
Anhydrous caffeine (JP15)
Anhydrous caffeine (JP16)
Anhydrous caffeine (TN)
ANOQUAN
ASPIRIN AND CAFFEINE W/ BUTALBITAL
Bayer Select Headache Pain
Berlin-Chemie Brand of Caffeine
BIDD:ER0554
BIDD:GT0632
BIDD:PXR0172
BIM-0050216.0001
Bio-0579
Bio1_000473
Bio1_000962
Bio1_001451
bmse000206
BRD-K02404261-001-02-7
BRD-K02404261-001-03-5
Bristol-Myers Squibb Brand of Caffeine
BRN 0017705
BSPBio_001921
BUTAL COMPOUND
BUTALBITAL ASPIRIN AND CAFFEINE
BUTALBITAL COMPOUND
BUTALBITAL W/ ASPIRIN & CAFFEINE
BUTALBITAL, ACETAMINOPHEN AND CAFFEINE
BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE
BUTALBITAL, ACETAMINOPHEN, CAFFEINE
BUTALBITAL, APAP, AND CAFFEINE
BUTALBITAL, ASPIRIN & CAFFEINE
BUTALBITAL, ASPIRIN AND CAFFEINE
BUTALBITAL, ASPIRIN, CAFFEINE, AND CODEINE PHOSPHATE
BUTALBITAL; ACETAMINOPHEN; AND CAFFEINE WITH CODEINE PHOSPHATE
C 0750
C07481
C0750_SIAL
c1094
C1778_SIAL
C2042
C6035_FLUKA
C6035_SIGMA
C7731_SIAL
C8960_SIAL
C8H10N4O2
Cafamil
Cafecon
Cafeina
cafeine
Cafergot
Caffedrine
Caffedrine Caplets
Caffein
Caffeina
Caffeina [Italian]
Caffeine
Caffeine (natural)
Caffeine (USP)
Caffeine Pure
Caffeine solution
Caffeine [BAN:JAN]
Caffeine, anhydrous
Caffeine, Monohydrate
Caffeine, synthetic
caffenium
Caffine
Cafipel
CCG-38825
CCRIS 1314
CFF
CHEBI:27732
CHEMBL113
Coffein
Coffein [German]
Coffeine
Coffeinum
Coffeinum N
Coffeinum Purrum
component of A.S.A. and Codeine Compound
component of A.S.A. Compound
component of Ansemco 2
component of Cafergot
component of Dilone
component of Midol
component of P-A-C Compound
component of Percobarb
component of Percodan
component of Phensal
COMPOUND 65
CU-01000012617-3
D002110
D00528
DARVON COMPOUND
DARVON COMPOUND-65
Dasin
DB00201
Dexitac
Dexitac Stay Alert Stimulant
DHC PLUS
DHCplus
Diurex
DivK1c_000730
Durvitan
EINECS 200-362-1
Eldiatric C
Enerjets
ERCATAB
ESGIC
ESGIC-PLUS
EU-0100228
EXCEDRIN (MIGRAINE)
FEMA No. 2224
FEMCET
FIORICET
FIORICET W/ CODEINE
FIORINAL
FIORINAL W/CODEINE NO 3
GlaxoSmithKline Brand of Caffeine
Guaranine
HMS1920I09
HMS2091O11
HMS2232M13
HMS3260N17
HMS502E12
HSDB 36
Hycomine
Hycomine Compound
I14-4386
IDI1_000730
INVAGESIC
INVAGESIC FORTE
KBio1_000730
KBio2_001781
KBio2_004349
KBio2_006917
KBio3_001141
KBioGR_002325
KBioSS_001781
Keep Alert
Kofein
Kofein [Czech]
Koffein
Koffein [German]
L000155
LANORINAL
Lopac-C-0750
Lopac0_000228
LS-237
Mateina
Maximum Strength Snapback Stimulant Powders
MEDIGESIC PLUS
MEGxp0_001350
Merck dura Brand of Caffeine
Methyltheobromide
Methyltheobromine
Methylxanthine theophylline
Mettler-Toledo(R) Calibration substance ME 18872, Caffeine
Midol Maximum Strength
MIGERGOT
Miudol
Mixture Name
MLS001055341
MLS001056714
MLS001066409
MolMap_000054
Monomethyl Derivative of Theophylline
Natural Caffeinum
NCGC00015208-01
NCGC00015208-02
NCGC00015208-03
NCGC00015208-04
NCGC00015208-05
NCGC00015208-06
NCGC00015208-07
NCGC00015208-08
NCGC00015208-09
NCGC00015208-10
NCGC00015208-11
NCGC00015208-12
NCGC00015208-13
NCGC00015208-14
NCGC00015208-15
NCGC00015208-16
NCGC00015208-17
NCGC00015208-18
NCGC00090699-01
NCGC00090699-02
NCGC00090699-03
NCGC00090699-04
NCGC00090699-05
NCGC00090699-06
NCGC00090699-07
NCGC00090699-08
NCGC00090699-09
NCGC00168808-01
NCGC00168808-02
nchembio.243-comp7
nchembio.63-comp5
nchembio774-comp2
NCI-C02733
NCIOpen2_008255
NINDS_000730
Nix Nap
No Doz
No-Doz
Nodaca
Nodoz Maximum Strength Caplets
Norgesic
NORGESIC FORTE
NSC 5036
NSC5036
Organex
ORPHENADRINE CITRATE, ASPIRIN, AND CAFFEINE
ORPHENGESIC
ORPHENGESIC FORTE
P-A-C Analgesic Tablets
Passauer Brand of Caffeine
PDSP1_001016
PDSP1_001235
PDSP2_001000
PDSP2_001219
Pep-Back
Percoffedrinol N
Percutaf?ine
Phensal
PHRENILIN WITH CAFFEINE AND CODEINE
Pierre Fabre Brand of Caffeine
Probes1_000150
Probes2_000128
Propoxyphene Compound 65
PROPOXYPHENE COMPOUND-65
PROPOXYPHENE HCL W/ ASPIRIN AND CAFFEINE
Quick Pep
Quick-Pep
Refresh'n
Republic Drug Brand of Caffeine
SBB006474
SDCCGMLS-0064595.P001
SDCCGMLS-0064595.P002
Seid Brand of Caffeine
SK 65 Compound
SK-65 Compound
SMR000326667
SPBio_001222
SPECTRUM1500155
Spectrum2_001261
Spectrum3_000321
Spectrum4_001782
Spectrum5_000423
Spectrum_001301
ST057528
Stim
STK177283
Synalgos
Synalgos-DC
SYNALGOS-DC-A
teina
Thein
Theine
Theobromine Me
Theobromine, 1-methyl-
Theophylline Me
Theophylline, 7-methyl
Thompson Brand 1 of Caffeine
Thompson Brand 2 of Caffeine
Tirend
TNP00310
Tri-Aqua
TRIAD
Ultra Pep-Back
UNII-3G6A5W338E
Vanquish
Vivarin
W222402_ALDRICH
Wake-Up
Wigraine
WLN: T56 BN DN FNVNVJ B1 F1 H1
Xanthine, 1,3,7-trimethyl
ZINC00001084
ATC-Codes:
Side-Effects:
Side-EffectFrequency
acidosis0
dry skin0
pulmonary edema0
hemorrhage0
gastrointestinal hemorrhage0
gastritis0
rash0
enterocolitis0
dyspnea0
cerebral hemorrhage0
sepsis0

Target

show target details
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:

015236952
016128907
109421
11990081
Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes.. W A Danie; M Syrek; Z Ry?ko; J Wˇjcikowski (2001) Polish journal of pharmacology display abstract
Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a considerable role. The aim of the present study was to investigate the influence of imipramine, amitriptyline and fluoxetine on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that imipramine exerted a most potent inhibitory effect on caffeine metabolism. Imipramine decreased the rate of 3-N-, 1-N- and 7-N-demethylations, and 8-hydroxylation of caffeine, the effect on 3-N-demethylation being most pronounced (Ki = 33 microM). Amitriptyline showed distinct inhibition of 3-N- and 1-N-demethylation of caffeine, though its effect was less potent than in the case of imipramine (Ki = 57 and 61 pM, respectively). The influence of amitriptyline on 8-hydroxylation and especially on 7-N-demethylation of caffeine was weaker (Ki = 108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a narrower spectrum of cytochrome P-450 inhibition by amitriptyline than by imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree--CYP3A. In contrast to the tested tricyclic antidepressants, fluoxetine did not exert any considerable effect on the 3-N- or 1-N-demethylation of caffeine (Ki = 152 and 196 microM, respectively), which indicates its low affinity for CYP1A2. However, fluoxetine displayed a clear inhibitory effect on caffeine 7-N-demethylation (Ki = 72 microM), the reaction which is catalyzed mainly by other than CYP1A2 isoenzymes. Fluoxetine diminished markedly the 8-hydroxylation of the marker drug; as reflected by Ki values, the potency of inhibition of rat CYP3A by fluoxetine was similar to that of imipramine (Ki = 40 and 45 microM, respectively). In summary, CYP1A2 was distinctly inhibited by imipramine and amitriptyline, CYP3A by imipramine and fluoxetine, while other CYP isoenzymes (CYP2B and/or 2E1) by imipramine and fluoxetine.
14586384
15529418
15659567
8474022
8818577
8880055
Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.. U Jeppesen; L F Gram; K Vistisen; S Loft; H E Poulsen; K Br°sen (1996) European journal of clinical pharmacology display abstract
OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. METHODS: The study was carried out as an in vivo single-dose study including 24 young, healthy men. All volunteers had been identified as sparteine- and mephenytoin-extensive metabolisers. The volunteers received in randomised order, at weekly intervals, increasing single oral doses of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6), mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals because of the long half-life of fluoxetine and its metabolite norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg and fluvoxamine was given in doses of 25, 50, 100 and 200 mg. RESULTS: With increasing doses, there was a statistically significant increase in the sparteine metabolic ratio (MR) (P < 0.01, Page's test for trend) for all four SSRIs. The increase was modest after intake of citalopram and fluvoxamine, while the increase was more pronounced after fluoxetine intake, although no volunteers changed phenotype from extensive metabolisers to poor metabolisers. Three of the six volunteers changed phenotype from extensive metabolisers to poor metabolisers after intake of 40 or 80 mg paroxetine. There was a statistically significant increase in the mephenytoin S/R ratio (P < 0.01, Page's test for trend) with increasing doses of fluoxetine and fluvoxamine, but not after citalopram and paroxetine. However, no volunteers changed phenotype from extensive to poor metabolisers of S-mephenytoin. After intake of fluvoxamine, the urinary excretion of the metabolites related to N3 demethylation of caffeine were below the limit of quantification, whereas there were no significant changes in the urinary caffeine metabolic ratios after intake of the other three SSRIs. CONCLUSION: This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account.
9152602
9351907
Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2.. M S Shet; M McPhaul; C W Fisher; N R Stallings; R W Estabrook (1997) Drug metabolism and disposition: the biological fate of chemicals display abstract
The antiandrogenic drug, flutamide, is widely used in the treatment of carcinoma of the prostate. The present study examines the metabolism of flutamide by human liver microsomes and purified recombinant human cytochrome P450s (CYP), expressed as fusion proteins. These studies show the principal role of CYP1A2 in the metabolism of flutamide to 2-hydroxyflutamide. A minor metabolite is formed during the metabolism of flutamide by CYP3A4 in the presence of an excess of added purified NADPH-P450 reductase. The metabolism of flutamide is inhibited by low concentrations of alpha-naphthoflavone and ketoconazole. Other substrates of CYP1A2, such as phenacetin, imipramine, caffeine, and estradiol, are also inhibitors of flutamide metabolism by CYP1A2. Of interest is the inhibition of flutamide metabolism by its metabolite, 2-hydroxyflutamide, and the inhibition of the 2- and 4- hydroxylation of estradiol by flutamide. CV1 cells do not metabolize flutamide to 2-hydroxyflutamide. In assays performed using this cell line transfected with the cDNA for the androgen receptor, flutamide is a pure antagonist, and 2-hydroxyflutamide, while a more potent androgen receptor (AR) antagonist, activates the AR at higher concentrations. Stable expression of CYPIA2 in these CV1 cells causes flutamide to exhibit agonistic properties at higher concentrations, a behavior not exhibited by cells stably transfected only with the expression vector encoding the AR. These findings raise the possibility that increased conversion of flutamide to 2-hydroxyflutamide or accumulation of 2-hydroxyflutamide in cells may contribute to the anomalous responses to flutamide that are observed in some advanced prostate cancers.
9764962
9855065