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Drug-Target Interaction

Drug

show drug details
PubChem ID:5361192
Structure:
Synonyms:
2-[(Z)-[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethana
5-Methoxy-4'-(trifluoromethyl)valerophenone (E)-O-(2-aminoethyl)oxime
AC1NSF25
BRD-K72676686-103-01-8
CAS-61718-82-9
Fluvoxamine
Lopac-F-2802
NCGC00015431-01
NCGC00015431-02
NCGC00018193-01
NCGC00018193-02
NCGC00018193-03
NCGC00021870-02
Tocris-1033
ATC-Codes:
Side-Effects:
Side-EffectFrequency
sweating increased1.0
malaise1.0
weight gain1.0
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
syncope0.086153835
amnesia0.086153835
hypotension0.086153835
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
hemorrhoids0.01
hypothyroidism0.01
heart failure0.01
tenosynovitis0.01
muscle spasm0.01
hypochondriasis0.01
seborrhea0.01
leukocytosis0.01
visual field defect0.01
hypercholesterolemia0.01
otitis media0.01
hypersomnia0.01
sleep disorder0.01
agoraphobia0.01
phobia0.01
cold extremities0.01
gait unsteady0.01
bursitis0.01
photosensitivity0.01
contracture0.01
hoarseness0.01
cardiomyopathy0.01
ulcer0.01
exfoliative dermatitis0.01
allergic reaction0.009999999
drug dependence0.009999999
abnormal gait0.009999999
arthralgia0.009999999
metrorrhagia0.009999999
rhinitis0.009999999
eructation0.009999999
urinary incontinence0.009999999
infection0.009999999
angina pectoris0.009999999
hypersensitivity0.009999999
dysuria0.009999999
ataxia0.009999999
back pain0.009999999
confusion0.009999999
suicide attempt0.009999999
peripheral edema0.009999999
postural hypotension0.009999999
migraine0.009999999
gastritis0.009999999
gastroenteritis0.009999999
increased salivation0.009999999
colitis0.009999999
hyperacusis0.009999999
pruritis0.009999999
hallucinations0.009999999
neck pain0.009999999
abnormal vision0.009999999
tetany0.009999999
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
gingivitis0.002999999
acne0.002999999
voice alteration0.0025000002
myocardial infarct0.0025000002
bradycardia0.0025
liver function test abnormal0.0024615387
diplopia0.0022857145
hemiplegia0.0022857145
dyskinesia0.0022857145
ear pain0.0022857145
thrombocytopenia0.0022857145
hiccups0.0022857145
gastrointestinal haemorrhage0.0022857145
psychosis0.0022857145
esophagitis0.0022857145
glossitis0.0022857145
stomatitis0.0022857145
delirium0.0022857145
eye pain0.0022857145
rectal haemorrhage0.0022857145
dry eyes0.0022857145
pneumonia0.0022857145
lymphadenopathy0.0022857145
paralysis0.0022857145
arthritis0.0022857145
anemia0.0022857145
breast pain0.0022857145
melena0.0022857145
neck rigidity0.0022857145
conjunctivitis0.0022857145
photophobia0.0022857145
cystitis0.0022857145
deafness0.0022857145
neuralgia0.0022857145
convulsion0.002285714
furunculosis0.0016923079
eczema0.0016923079
urticaria0.0016923076
dry skin0.0016923076
alopecia0.0016923076
agranulocytosis0.0010
hyperglycemia0.0010
tenesmus0.0010
leukopenia0.0010
carcinoma0.0010
cholelithiasis0.0010
pulmonary disease0.0010
serotonin syndrome0.0010
bone pain0.0010
hyperesthesia0.0010
lactate dehydrogenase increased0.0010
herpes zoster0.0010
coma0.0010
mouth ulceration0.0010
hematospermia0.0010
herpes simplex0.0010
pathological fracture0.0010
corneal ulcer0.0010
blepharitis0.0010
leg cramps0.0010
av block0.0010
myopathy0.0010
amenorrhea0.0010
anaphylactic reaction0.0010
hypokalemia0.0010
aplastic anemia0.0010
hypoglycemia0.0010
apnea0.0010
tardive dyskinesia0.0010
arrhythmia0.0010
jaundice0.0010
kidney pain0.0010
hyperlipidemia0.0010
kidney calculus0.0010
neuropathy0.0010
acute renal failure0.0010
rheumatoid arthritis0.0010
lacrimation disorder0.0010
urinary urgency0.0010
retinal detachment0.0010
pericarditis0.0010
embolus0.0010
hematemesis0.0010
toxic epidermal necrolysis0.0010
phlebitis0.0010
hyponatremia0.0010
porphyria0.0010
fecal incontinence0.0010
supraventricular extrasystoles0.0010
cerebrovascular accident0.0010
priapism0.0010
stevens - johnson syndrome0.0010
halitosis0.0010
psoriasis0.0010
purpura0.0010
shock0.0010
goiter0.0010
torticollis0.0010
cholecystitis0.0010
pelvic pain0.0010
obesity0.0010
nocturia0.0010
hepatitis0.0010
hernia0.0010
cyst0.0010
neoplasia0.0010
peripheral vascular disorder0.0010
coronary artery disease0.0010
diabetes mellitus0.0010
haemorrhage0.0010
dysmenorrhea0.0010
hematuria0.0010
pancreatitis0.0010
hemoptysis0.0010
vaginitis0.0010
vasculitis0.0010
ventricular tachycardia0.0010
dysarthria0.0010
stupor0
thinking abnormal0
depersonalization0
emotional lability0
apathy0
delusions0
euphoria0
siadh0
pms0
galactorrhea0
herpes0
major depressive disorder0
tinnitus0
fatigue0
vaginal hemorrhage0
sexual dysfunction0
manic0

Target

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Uniprot ID:CP2CJ_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC17
CYPIIC19
Cytochrome P450 2C19
Mephenytoin 4-hydroxylase
P450-11A
P450-254C
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

012695344
015025747
12695344
Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19.. Caiping Yao; Kent L Kunze; William F Trager; Evan D Kharasch; RenÚ H Levy (2003) Drug metabolism and disposition: the biological fate of chemicals display abstract
A previous study suggested that fluvoxamine inhibition potency toward CYP1A2 is 10 times greater in vivo than in vitro. The present study was designed to determine whether the same gap exists for CYP2C19, another isozyme inhibited by fluvoxamine. In vitro studies examined the effect of nonspecific binding on the determination of inhibition constant (K(i)) values of fluvoxamine toward CYP2C19 in human liver microsomes and in a cDNA-expressed microsomal (Supersomes) system using (S)-mephenytoin as a CYP2C19 probe. K(i) values based on total added fluvoxamine concentration (K(i,total)) and unbound fluvoxamine concentration (K(i,ub)) were calculated, and interindividual variability in K(i) values was examined in six nonfatty livers. K(i,total) values varied with microsomal protein concentration, whereas the corresponding K(i,ub) values were within a narrow range (70-80 nM). In vivo inhibition constants (K(i)iv) were obtained from a study of the disposition of a single oral dose (100 mg) of the CYP2C19 probe (S)-mephenytoin in 12 healthy volunteers receiving fluvoxamine at 0, 37.5, 62.6, and 87.5 mg/day to steady state. In this population, the ratio of (S)-4-hydroxy-mephenytoin formation clearances (uninhibited/inhibited) was positively correlated with fluvoxamine average steady-state concentration with an intercept of 0.85 (r(2) = 0.88, p < 0.001). The mean (+/-S.D.) values of K(i)iv based on total and unbound plasma concentrations were 13.5 +/- 5.6 and 1.9 +/- 1.1 nM, respectively. Comparison of in vitro and in vivo K(i) values, based on unbound fluvoxamine concentrations, suggests that fluvoxamine inhibition potency is roughly 40 times greater in vivo than in vitro.
15199661
17596106
Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide.. Oliver von Richter; Gezim Lahu; Andreas Huennemeyer; Rolf Herzog; Karl Zech; Robert Hermann (2007) Clinical pharmacokinetics display abstract
OBJECTIVE: To investigate the effects of steady-state dosing of fluvoxamine, an inhibitor of cytochrome P450 (CYP) 1A2 and CYP2C19, on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor and its pharmacodynamically active metabolite roflumilast N-oxide. METHODS: In an open-label, non-randomised, one-sequence, two-period, two-treatment crossover study, 14 healthy subjects received a single oral dose of roflumilast 500 microg on study day 1. After a 6-day washout period, repeated doses of fluvoxamine 50 mg once daily were given from days 8 to 21. On day 15, roflumilast 500 microg and fluvoxamine 50 mg were taken concomitantly. Percentage ratios of test/reference (reference: roflumilast alone; test: roflumilast plus steady-state fluvoxamine) of geometric means and their 90% confidence intervals for area under the plasma concentration-time curve, maximum plasma concentration (roflumilast and roflumilast N-oxide) and plasma clearance of roflumilast were calculated. RESULTS: Upon co-administration with steady-state fluvoxamine, the exposure to roflumilast as well as roflumilast N-oxide increased by a factor of 2.6 and 1.5, respectively. Roflumilast plasma clearance decreased by a factor of 2.6, from 9.06 L/h (reference) to 3.53 L/h (test). The combined effect of fluvoxamine co-administration on roflumilast and roflumilast N-oxide exposures resulted in a moderate (i.e. 59%) increase in total PDE4 inhibitory activity. CONCLUSION: Co-administration of roflumilast and fluvoxamine affects the disposition of roflumilast and its active metabolite roflumilast N-oxide most likely via a potent dual pathway inhibition of CYP1A2 and CYP2C19 by fluvoxamine. The exposure increases observed for roflumilast N-oxide are suggested to be attributable to CYP2C19 co-inhibition by fluvoxamine and thus, are not to be expected to occur when roflumilast is co-administered with more selective CYP1A2 inhibitors.