Home
Drugs
Targets
Pathways
Ontologies
Cyp450s
Adv.search
Help/FAQ

Drug-Target Interaction

Drug

show drug details
PubChem ID:3404
Structure:
Synonyms:
2-[[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethanamine
AC1L1FUZ
DB00176
Fluvoxamina [Inn-Spanish]
Fluvoxamine
Fluvoxamine maleate
Fluvoxaminum [Inn-Latin]
Prestwick0_000995
Prestwick1_000995
SPBio_002980
ATC-Codes:
Side-Effects:
Side-EffectFrequency
sweating increased1.0
weight gain1.0
malaise1.0
vertigo0.85857147
palpitations0.6426315
constipation0.63500005
tremor0.5928572
abdominal pain0.5273913
nausea0.51354843
agitation0.4896001
insomnia0.47599998
headache0.475
somnolence0.4593549
dry mouth0.45310357
nervousness0.44827592
vomiting0.447143
asthenia0.4374195
dyspepsia0.42966685
anorexia0.42466673
dizziness0.42451614
diarrhea0.42322582
anxiety0.40612903
weight loss0.13499999
upper respiratory infection0.09
tachycardia0.08615385
amnesia0.086153835
hypotension0.086153835
syncope0.086153835
hypertension0.081428565
sinusitis0.07923079
cough0.07923078
edema0.07784618
sweating0.062222224
abscess0.03
toothache0.03
blurred vision0.03
urinary frequency0.020000001
amblyopia0.02
viral infection0.02
flatulence0.019999998
flu syndrome0.016666668
myalgia0.015714284
libido decreased0.015652176
impotence0.014999999
pharyngitis0.013846155
dysphagia0.013333333
dyspnea0.013333332
chest pain0.01153846
paresthesia0.01142857
tooth disorder0.011157895
neurosis0.010769229
hypochondriasis0.01
muscle spasm0.01
visual field defect0.01
hemorrhoids0.01
leukocytosis0.01
hypercholesterolemia0.01
hypothyroidism0.01
otitis media0.01
hoarseness0.01
heart failure0.01
tenosynovitis0.01
seborrhea0.01
ulcer0.01
contracture0.01
phobia0.01
gait unsteady0.01
cold extremities0.01
sleep disorder0.01
cardiomyopathy0.01
exfoliative dermatitis0.01
hypersomnia0.01
bursitis0.01
agoraphobia0.01
photosensitivity0.01
back pain0.009999999
colitis0.009999999
ataxia0.009999999
pruritis0.009999999
arthralgia0.009999999
abnormal gait0.009999999
metrorrhagia0.009999999
infection0.009999999
hypersensitivity0.009999999
angina pectoris0.009999999
postural hypotension0.009999999
drug dependence0.009999999
neck pain0.009999999
dysuria0.009999999
hallucinations0.009999999
eructation0.009999999
suicide attempt0.009999999
tetany0.009999999
allergic reaction0.009999999
peripheral edema0.009999999
confusion0.009999999
gastritis0.009999999
abnormal vision0.009999999
hyperacusis0.009999999
rhinitis0.009999999
urinary incontinence0.009999999
migraine0.009999999
increased salivation0.009999999
gastroenteritis0.009999999
pain0.009071431
chills0.0084
arthrosis0.0077499994
ecchymosis0.0070
angioedema0.0060
urinary retention0.0054999986
menorrhagia0.0051428564
bronchitis0.004666667
laryngitis0.004615383
fever0.0044838707
eruption0.0043750005
epistaxis0.0042857137
urinary tract infection0.0037142858
polyuria0.0037142858
asthma0.0035714284
dehydration0.00325
acne0.002999999
gingivitis0.002999999
myocardial infarct0.0025000002
voice alteration0.0025000002
bradycardia0.0025
liver function test abnormal0.0024615387
deafness0.0022857145
dyskinesia0.0022857145
pneumonia0.0022857145
ear pain0.0022857145
psychosis0.0022857145
thrombocytopenia0.0022857145
esophagitis0.0022857145
stomatitis0.0022857145
gastrointestinal haemorrhage0.0022857145
glossitis0.0022857145
anemia0.0022857145
diplopia0.0022857145
paralysis0.0022857145
lymphadenopathy0.0022857145
arthritis0.0022857145
dry eyes0.0022857145
rectal haemorrhage0.0022857145
neck rigidity0.0022857145
conjunctivitis0.0022857145
photophobia0.0022857145
cystitis0.0022857145
delirium0.0022857145
hemiplegia0.0022857145
melena0.0022857145
hiccups0.0022857145
breast pain0.0022857145
neuralgia0.0022857145
eye pain0.0022857145
convulsion0.002285714
eczema0.0016923079
furunculosis0.0016923079
urticaria0.0016923076
alopecia0.0016923076
dry skin0.0016923076
leg cramps0.0010
bone pain0.0010
hepatitis0.0010
hyperlipidemia0.0010
leukopenia0.0010
coma0.0010
mouth ulceration0.0010
hematospermia0.0010
pulmonary disease0.0010
serotonin syndrome0.0010
corneal ulcer0.0010
urinary urgency0.0010
coronary artery disease0.0010
peripheral vascular disorder0.0010
cyst0.0010
dysmenorrhea0.0010
cholelithiasis0.0010
kidney pain0.0010
arrhythmia0.0010
apnea0.0010
tardive dyskinesia0.0010
aplastic anemia0.0010
hyponatremia0.0010
phlebitis0.0010
anaphylactic reaction0.0010
amenorrhea0.0010
agranulocytosis0.0010
jaundice0.0010
hypokalemia0.0010
neuropathy0.0010
carcinoma0.0010
blepharitis0.0010
tenesmus0.0010
hypoglycemia0.0010
av block0.0010
lacrimation disorder0.0010
acute renal failure0.0010
rheumatoid arthritis0.0010
kidney calculus0.0010
myopathy0.0010
lactate dehydrogenase increased0.0010
hyperglycemia0.0010
pericarditis0.0010
halitosis0.0010
retinal detachment0.0010
goiter0.0010
obesity0.0010
shock0.0010
nocturia0.0010
pathological fracture0.0010
stevens - johnson syndrome0.0010
herpes simplex0.0010
purpura0.0010
haemorrhage0.0010
hemoptysis0.0010
pancreatitis0.0010
hematuria0.0010
porphyria0.0010
supraventricular extrasystoles0.0010
priapism0.0010
hematemesis0.0010
pelvic pain0.0010
psoriasis0.0010
cerebrovascular accident0.0010
fecal incontinence0.0010
vaginitis0.0010
vasculitis0.0010
cholecystitis0.0010
torticollis0.0010
neoplasia0.0010
ventricular tachycardia0.0010
diabetes mellitus0.0010
dysarthria0.0010
herpes zoster0.0010
hernia0.0010
hyperesthesia0.0010
toxic epidermal necrolysis0.0010
embolus0.0010
major depressive disorder0
delusions0
siadh0
pms0
depersonalization0
stupor0
apathy0
euphoria0
vaginal hemorrhage0
thinking abnormal0
galactorrhea0
herpes0
fatigue0
tinnitus0
emotional lability0
sexual dysfunction0
manic0

Target

show target details
Uniprot ID:CP2C9_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC9
Cytochrome P450 2C9
P-450MP
P450 MP-4/MP-8
P450 PB-1
S-mephenytoin 4-hydroxylase
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:1OG2 1OG5 1R9O
Structure:
1R9O

Binding Affinities:

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

References:

011180037
011206048
10192756
Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies with tolbutamide and (S)-warfarin using human liver microsomes.. A Hemeryck; C De Vriendt; F M Belpaire (1999) European journal of clinical pharmacology display abstract
OBJECTIVE: To investigate the in vitro potential of selective serotonin reuptake inhibitors (SSRIs) to inhibit two CYP2C9-catalysed reactions, tolbutamide 4-methylhydroxylation and (S)-warfarin 7-hydroxylation. METHODS: The formation of 4-hydroxytolbutamide from tolbutamide and that of 7-hydroxywarfarin from (S)-warfarin as a function of different concentrations of SSRIs and some of their metabolites was studied in microsomes from three human livers. RESULTS: Both tolbutamide 4-methylhydroxylation and (S)-warfarin 7-hydroxylation followed one enzyme Michaelis-Menten kinetics. Kinetic analysis of 4-hydroxytolbutamide formation yielded a mean apparent Michaelis-Menten constant (Km) of 133 microM and a mean apparent maximal velocity (Vmax) of 248 pmol x min(-1) x mg(-1); formation of 7-hydroxywarfarin yielded a mean Km of 3.7 microM and a mean Vmax of 10.5 pmol x min(-1) x mg(-1). Amongst the SSRIs and some of their metabolites tested, only fluvoxamine markedly inhibited both reactions. The average computed inhibition constant (Ki) values and ranges of fluvoxamine when tolbutamide and (S)-warfarin were used as substrate, were 13.3 (6.4-17.3) microM and 13.0 (8.4-18.7) microM, respectively. The average Ki value of fluoxetine for (S)-warfarin 7-hydroxylation was 87.0 (57.0-125) microM. CONCLUSION: Amongst the SSRIs tested, fluvoxamine was shown to be the most potent inhibitor of both tolbutamide 4-methylhydroxylation and (S)-warfarin 7-hydroxylation. Fluoxetine, norfluoxetine, paroxetine, sertraline, desmethylsertraline, citalopram, desmethylcitalopram had little or no effect on CYP2C9 activity in vitro. This is consistent with in vivo data indicating that amongst the SSRIs, fluvoxamine has the greatest potential for inhibiting CYP2C9-mediated drug metabolism.
11180037
Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide.. H Madsen; T P Enggaard; L L Hansen; N A Klitgaard; K BrÝsen (2001) Clinical pharmacology and therapeutics display abstract
OBJECTIVE: Our objective was to examine the interaction between fluvoxamine and tolbutamide to confirm that fluvoxamine inhibits CYP2C9. METHODS: The study was carried out as an open, randomized, crossover design with 14 healthy participants. In period A, all volunteers took 500 mg of tolbutamide orally. In period B, the volunteers were randomly assigned to one of two groups. Each group took either 150 mg or 75 mg of fluvoxamine a day for 5 days (day -3 to day 2). The groups then took 500 mg of tolbutamide as a single dose (day 0). In both periods, blood and urine were sampled at regular intervals. Plasma was analyzed for tolbutamide, and urine was analyzed for tolbutamide and its two metabolites, 4-hydroxytolbutamide and carboxytolbutamide by means of HPLC. RESULTS: During treatment with fluvoxamine, there was a statistically significant decrease in the median of the total clearance of tolbutamide, from 845 mL/h to 688 mL/h, among the volunteers who received 75 mg/d. There was a reduction that reached borderline statistical significance in the group that received 150 mg/d of tolbutamide. The clearance by means of 4-hydroxytolbutamide and carboxytolbutamide was significantly reduced in both groups (ie, from 901 mL/h to 318 mL/h in the group that received 150 mg of tolbutamide per day and from 723 mL/h to 457 mL/h in the group that received 75 mg of tolbutamide per day). Thus there was a tendency toward a more pronounced inhibition of the 4-hydroxylation during treatment with 150 mg/d of fluvoxamine compared with 75 mg/d, but the difference was not statistically significant. CONCLUSION: Fluvoxamine is a moderate inhibitor of CYP2C9 in vivo.
15199661