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Drug-Target Interaction

Drug

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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: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:

7974626
Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service.. M Jerling; L Lindstr÷m; U Bondesson; L Bertilsson (1994) Therapeutic drug monitoring display abstract
Therapeutic drug monitoring data for clozapine were used to study interactions with other drugs. The distribution of the ratio concentration/dose (C/D) of clozapine was compared in four matched groups--patients simultaneously treated with benzodiazepines, patients on drugs that inhibit the cytochrome P450 enzyme CYP2D6, patients taking carbamazepine, and those not taking any of these drugs. No difference was seen among the monotherapy, CYP2D6, and benzodiazepine groups. Patients on carbamazepine had a mean 50% lower C/D than the monotherapy group (p < 0.001), indicating that carbamazepine is an inducer of the metabolism of clozapine. The C/D was inversely correlated to the daily dose of carbamazepine. Intraindividual comparisons in eight patients, with analyses both on and off carbamazepine, confirmed a substantial decrease of the clozapine concentration when carbamazepine was introduced. Four patients treated with clozapine were concomitantly given the antidepressant fluvoxamine. Three of them exhibited a much higher C/D ratio when on fluvoxamine compared with the monotherapy group. Two had their clozapine levels analyzed when on and off fluvoxamine. The dose-normalized clozapine concentration increased by a factor of 5-10 when fluvoxamine was added. We conclude that carbamazepine causes decreased clozapine plasma levels, while fluvoxamine increases the levels. The pathways are not known with certainty, but CYP1A2 may be of major importance for the metabolism of clozapine, since fluvoxamine is a potent inhibitor of this enzyme. A recent panel study suggests that determination of CYP1A2 activity with the caffeine test may be very useful for the dosing of clozapine. The induction of clozapine metabolism by carbamazepine might be partly mediated by CYP3A4.
9205822
Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2.. S E Ball; D Ahern; J Scatina; J Kao (1997) British journal of clinical pharmacology display abstract
AIMS: In order to anticipate drug-interactions of potential clinical significance the ability of the novel antidepressant, venlafaxine, to inhibit CYP2D6 dependent imipramine and desipramine 2-hydroxylation was investigated in human liver microsomes. The data obtained were compared with the selective serotonin re-uptake inhibitors, fluoxetine, sertraline, fluvoxamine and paroxetine. Venlafaxine's potential to inhibit several other major P450 s was also studied (CYP3A4, CYP2D6, CYP1A2). METHODS: Ki values for venlafaxine, paroxetine, fluoxetine, fluvoxamine and sertraline as inhibitors of imipramine and desipramine 2-hydroxylation were determined from Dixon plots of control and inhibited rate data in human hepatic microsomal incubations. The inhibitory effect of imipramine and desipramine on liver microsomal CYP2D6 dependent venlafaxine O-demethylation was determined similarly. Venlafaxine's IC50 values for CYP3A4, CYP1A2 CYP2C9 were determined based on inhibition of probe substrate activities (testosterone 6 beta-hydroxylation, ethoxyresorufin O-dealkylase and tolbutamide 4-hydroxylation, respectively). RESULTS: Fluoxetine, paroxetine, and fluvoxamine were potent inhibitors of imipramine 2-hydroxylase activity (Ki values of 1.6 +/- 0.8, 3.2 +/- 0.8 and 8.0 +/- 4.3 microM, respectively; mean +/- s.d., n = 3), while sertraline was less inhibitory (Ki of 24.7 +/- 8.9 microM). Fluoxetine also markedly inhibited desipramine 2-hydroxylation with a Ki of 1.3 +/- 0.5 microM. Venlafaxine was less potent an inhibitor of imipramine 2-hydroxylation (Ki of 41.0 +/- 9.5 microM) than the SSRIs that were studied. Imipramine and desipramine gave marked inhibition of CYP2D6 dependent venlafaxine O-demethylase activity (Ki values of 3.9 +/- 1.7 and 1.7 +/- 0.9 microM, respectively). Venlafaxine did not inhibit ethoxyresorufin O-dealkylase (CYP1A2), tolbutamide 4-hydroxylase (CYP2C9) or testosterone 6 beta-hydroxylase (CYP3A4) activities at concentrations of up to 1 mM. CONCLUSIONS: It is concluded that venlafaxine has a low potential to inhibit the metabolism of substrates for CYP2D6 such as imipramine and desipramine compared with several of the most widely used SSRIs, as well as the metabolism of substrates for several of the other major human hepatic P450s.
9757149
Effect of fluvoxamine therapy on the activities of CYP1A2, CYP2D6, and CYP3A as determined by phenotyping.. A D Kashuba; A N Nafziger; G L Kearns; J S Leeder; R Gotschall; M L RocciJr; R W Kulawy; D J Beck; J S BertinoJr (1998) Clinical pharmacology and therapeutics display abstract
OBJECTIVE: To determine the effect of 150 mg/day fluvoxamine on the activities of CYP1A2, CYP2D6, CYP3A, N-acetyltransferase-2 (NAT2), and xanthine oxidase (XO) by phenotyping with caffeine, dextromethorphan, and midazolam. METHODS: Oral caffeine (2 mg/kg), oral dextromethorphan (30 mg), and intravenous midazolam (0.025 mg/kg) were administered to 10 white male volunteers every 14 days for 4 months and to 10 white premenopausal female volunteers during the midfollicular and midluteal phases of the menstrual cycle for 4 complete cycles (8 total phenotyping measures). The first 6 phenotyping measures were used to establish baseline activity. Subjects were given 150 mg/day fluvoxamine for the fourth month or cycle of the study. Enzyme activity for CYP1A2, CYP2D6, NAT2, and XO was expressed as urinary metabolite ratios. Midazolam plasma clearance was used to express CYP3A activity. RESULTS: No difference between baseline and weeks 2 and 4 of fluvoxamine therapy was observed for NAT2 or XO metabolite ratios. For CYP1A2, CYP2D6, and CYP3A phenotypes, significant differences existed between baseline and fluvoxamine therapy. For CYP1A2, the mean urinary metabolite ratio (+/-SD) was 7.53 +/- 7.44 at baseline and 4.30 +/- 2.82 with fluvoxamine ( P = .012). Mean CYP2D6 molar urinary dextromethorphan ratios before and after fluvoxamine therapy were 0.00780 +/- 0.00694 and 0.0153 +/- 0.0127, respectively (P = .011). Midazolam clearance decreased from 0.0081 +/ 0.0024 L/min/kg at baseline to 0.0054 +/- 0.0021 L/min/kg with therapy (P = .0091). For CYP1A2, CYP2D6, and CYP3A, fluvoxamine therapy changed the phenotyping measures by a median of -44.4%, 123.5%, and -34.4%, respectively. CONCLUSIONS: We concluded that fluvoxamine may cause significant inhibition of CYP1A2, CYP2D6, and CYP3A activity. This metabolic inhibition may have serious implications for a variety medications.