Identification

Name
Nefazodone
Accession Number
DB01149  (APRD00402)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States.

Structure
Thumb
Synonyms
  • 1-(3-(4-(m-Chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-delta2-1,2,4-triazolin-5-one
  • Nefazodona
  • Nefazodone
  • Nefazodonum
Product Ingredients
IngredientUNIICASInChI Key
Nefazodone Hydrochloride27X63J94GR82752-99-6DYCKFEBIOUQECE-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nefazodone hydrochlorideTablet250 mg/1OralRanbaxy Inc.2008-12-24Not applicableUs
Nefazodone hydrochlorideTablet100 mg/1OralRanbaxy Inc.2008-12-24Not applicableUs
Nefazodone hydrochlorideTablet200 mg/1OralRanbaxy Inc.2008-12-24Not applicableUs
Nefazodone hydrochlorideTablet50 mg/1OralRanbaxy Inc.2008-12-24Not applicableUs
Nefazodone hydrochlorideTablet150 mg/1OralRanbaxy Inc.2008-12-24Not applicableUs
SerzoneTablet150 mg/1OralBristol Myers Squibb2006-01-012007-09-30Us
SerzoneTablet50 mg/1OralBristol Myers Squibb2004-01-012005-08-05Us
SerzoneTablet250 mg/1OralBristol Myers Squibb2005-01-012006-12-31Us
SerzoneTablet150 mg/1OralPhysicians Total Care, Inc.1994-12-221997-12-31Us
SerzoneTablet200 mg/1OralBristol Myers Squibb2006-01-012007-10-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lin-nefazodoneTablet200 mgOralLinson Pharma Co.2000-09-112003-11-28Canada
Lin-nefazodoneTablet50 mgOralLinson Pharma Co.2000-09-112003-11-28Canada
Lin-nefazodoneTablet150 mgOralLinson Pharma Co.2000-09-112003-11-28Canada
Lin-nefazodoneTablet100 mgOralLinson Pharma Co.2000-09-112003-11-28Canada
Nefazodone HydrochlorideTablet250 mg/1OralPreferreed Pharmaceuticals Inc.2018-08-14Not applicableUs
Nefazodone HydrochlorideTablet250 mg/1Oralbryant ranch prepack2003-09-16Not applicableUs
Nefazodone HydrochlorideTablet100 mg/1OralRemedy Repack2011-06-082011-06-09Us
Nefazodone HydrochlorideTablet250 mg/1OralTeva Pharmaceuticals USA, Inc.2003-09-16Not applicableUs0093 102620180814 13942 1wj1roh
Nefazodone HydrochlorideTablet100 mg/1OralStat Rx USA2010-08-18Not applicableUs
Nefazodone HydrochlorideTablet100 mg/1OralTeva Pharmaceuticals USA, Inc.2003-09-16Not applicableUs00093 1024 06 nlmimage10 8e29c77e
International/Other Brands
Dutonin / Serzone
Categories
UNII
59H4FCV1TF
CAS number
83366-66-9
Weight
Average: 470.007
Monoisotopic: 469.224453
Chemical Formula
C25H32ClN5O2
InChI Key
VRBKIVRKKCLPHA-UHFFFAOYSA-N
InChI
InChI=1S/C25H32ClN5O2/c1-2-24-27-31(25(32)30(24)18-19-33-23-10-4-3-5-11-23)13-7-12-28-14-16-29(17-15-28)22-9-6-8-21(26)20-22/h3-6,8-11,20H,2,7,12-19H2,1H3
IUPAC Name
1-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-3-ethyl-4-(2-phenoxyethyl)-4,5-dihydro-1H-1,2,4-triazol-5-one
SMILES
CCC1=NN(CCCN2CCN(CC2)C2=CC(Cl)=CC=C2)C(=O)N1CCOC1=CC=CC=C1

Pharmacology

Indication

For the treatment of depression.

Associated Conditions
Pharmacodynamics

Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.

Mechanism of action

Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Human
A5-hydroxytryptamine receptor 2C
antagonist
Human
ASodium-dependent serotonin transporter
inhibitor
Human
A5-hydroxytryptamine receptor 1A
antagonist
Human
ASodium-dependent noradrenaline transporter
inhibitor
Human
USodium-dependent dopamine transporter
inhibitor
Human
UAlpha-1B adrenergic receptor
other/unknown
Human
UAlpha-2A adrenergic receptor
antagonist
Human
NAlpha-1A adrenergic receptor
antagonist
Human
UPotassium voltage-gated channel subfamily H member 2
antagonist
Human
Absorption

Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%).

Volume of distribution
  • 0.22 to 0.87 L/kg
Protein binding

Greater than 99% (in vitro, human plasma proteins).

Metabolism

Hepatic.

Route of elimination

Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine.

Half life

2-4 hours

Clearance
Not Available
Toxicity

Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Nefazodone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Nefazodone.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Nefazodone is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Nefazodone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Nefazodone.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Nefazodone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Nefazodone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Nefazodone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Nefazodone.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Nefazodone.
Food Interactions
  • Avoid alcohol.
  • Avoid avocado.
  • Limit garlic, ginger, gingko, and horse chestnut.
  • Take this medication either consistently with or without food as instructed by your doctor.

References

Synthesis Reference
US4338317
General References
  1. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. [PubMed:9098663]
External Links
Human Metabolome Database
HMDB0015280
KEGG Compound
C07256
PubChem Compound
4449
PubChem Substance
46508323
ChemSpider
4294
BindingDB
50069447
ChEBI
7494
ChEMBL
CHEMBL623
Therapeutic Targets Database
DAP000042
PharmGKB
PA450603
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nefazodone
ATC Codes
N06AX06 — Nefazodone
FDA label
Download (152 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentCocaine-Related Disorders1
2CompletedTreatmentCocaine-Related Disorders / Substance-Related Disorders1
2CompletedTreatmentMarijuana Abuse1
3CompletedTreatmentCocaine-Related Disorders1
4CompletedTreatmentSocial Anxiety Disorder (SAD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • AQ Pharmaceuticals Inc.
  • Bristol-Myers Squibb Co.
  • Direct Dispensing Inc.
  • Doctor Reddys Laboratories Ltd.
  • Eon Labs
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Pharma Pac LLC
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Va Cmop Dallas
Dosage forms
FormRouteStrength
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral200 mg/1
TabletOral250 mg/1
TabletOral50 mg/1
TabletOral100 mg
TabletOral150 mg
TabletOral200 mg
TabletOral50 mg
Prices
Unit descriptionCostUnit
Nefazodone hcl 250 mg tablet1.82USD tablet
Nefazodone hcl 200 mg tablet1.78USD tablet
Nefazodone hcl 150 mg tablet1.75USD tablet
Nefazodone hcl 100 mg tablet1.72USD tablet
Nefazodone hcl 50 mg tablet1.68USD tablet
Serzone 100 mg tablet1.53USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)83.5 °CPhysProp
logP4.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0698 mg/mLALOGPS
logP3.71ALOGPS
logP4.65ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)7.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area51.62 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity132.38 m3·mol-1ChemAxon
Polarizability51.85 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9744
Caco-2 permeable+0.5296
P-glycoprotein substrateSubstrate0.5809
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.8373
Renal organic cation transporterInhibitor0.5685
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.7506
CYP450 1A2 substrateNon-inhibitor0.7931
CYP450 2C9 inhibitorInhibitor0.5999
CYP450 2D6 inhibitorNon-inhibitor0.8799
CYP450 2C19 inhibitorNon-inhibitor0.5434
CYP450 3A4 inhibitorNon-inhibitor0.8711
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8028
Ames testNon AMES toxic0.5208
CarcinogenicityNon-carcinogens0.7388
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9067 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8749
hERG inhibition (predictor II)Inhibitor0.7288
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0uk9-9846000000-49cb6e97c09a9e806dd5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0260900000-3ebf8f0b9eda5fea1378
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-3790200000-9f64b1295a633dcdd772

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aniline and substituted anilines / Dialkylarylamines / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Chlorobenzenes / N-alkylpiperazines / Aryl chlorides / Heteroaromatic compounds
show 7 more
Substituents
Phenylpiperazine / N-arylpiperazine / Phenol ether / Tertiary aliphatic/aromatic amine / Phenoxy compound / Dialkylarylamine / Aniline or substituted anilines / Chlorobenzene / N-alkylpiperazine / Halobenzene
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, N-arylpiperazine, monochlorobenzenes, N-alkylpiperazine, triazoles (CHEBI:7494)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Hidalgo R, Hertzberg MA, Mellman T, Petty F, Tucker P, Weisler R, Zisook S, Chen S, Churchill E, Davidson J: Nefazodone in post-traumatic stress disorder: results from six open-label trials. Int Clin Psychopharmacol. 1999 Mar;14(2):61-8. [PubMed:10220119]
  2. Meyer JH, Cho R, Kennedy S, Kapur S: The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET. Psychopharmacology (Berl). 1999 Jun;144(3):279-81. [PubMed:10435395]
  3. Horton JC, Trobe JD: Akinetopsia from nefazodone toxicity. Am J Ophthalmol. 1999 Oct;128(4):530-1. [PubMed:10577608]
  4. Eckler JR, Rabin RA, Winter JC: Nefazodone in the rat: mimicry and antagonism of [-]-DOM-induced stimulus control. Pharmacol Biochem Behav. 2003 May;75(2):405-10. [PubMed:12873632]
  5. Avila A, Cardona X, Martin-Baranera M, Maho P, Sastre F, Bello J: Does nefazodone improve both depression and Parkinson disease? A pilot randomized trial. J Clin Psychopharmacol. 2003 Oct;23(5):509-13. [PubMed:14520130]
  6. Taylor DP, Carter RB, Eison AS, Mullins UL, Smith HL, Torrente JR, Wright RN, Yocca FD: Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry. 1995;56 Suppl 6:3-11. [PubMed:7649970]
  7. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  8. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. [PubMed:9098663]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Millan MJ: Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60. [PubMed:16433010]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Owens MJ, Ieni JR, Knight DL, Winders K, Nemeroff CB: The serotonergic antidepressant nefazodone inhibits the serotonin transporter: in vivo and ex vivo studies. Life Sci. 1995;57(24):PL373-80. [PubMed:7475971]
  2. Narayan M, Anderson G, Cellar J, Mallison RT, Price LH, Nelson JC: Serotonin transporter-blocking properties of nefazodone assessed by measurement of platelet serotonin. J Clin Psychopharmacol. 1998 Feb;18(1):67-71. [PubMed:9472845]
  3. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  4. Taylor DP, Carter RB, Eison AS, Mullins UL, Smith HL, Torrente JR, Wright RN, Yocca FD: Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry. 1995;56 Suppl 6:3-11. [PubMed:7649970]
  5. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. [PubMed:9098663]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Owens MJ, Ieni JR, Knight DL, Winders K, Nemeroff CB: The serotonergic antidepressant nefazodone inhibits the serotonin transporter: in vivo and ex vivo studies. Life Sci. 1995;57(24):PL373-80. [PubMed:7475971]
  2. Owen D, Du L, Bakish D, Lapierre YD, Hrdina PD: Norepinephrine transporter gene polymorphism is not associated with susceptibility to major depression. Psychiatry Res. 1999 Jul 30;87(1):1-5. [PubMed:10512149]
  3. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  4. Taylor DP, Carter RB, Eison AS, Mullins UL, Smith HL, Torrente JR, Wright RN, Yocca FD: Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry. 1995;56 Suppl 6:3-11. [PubMed:7649970]
  5. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. [PubMed:9098663]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  3. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Taylor DP, Carter RB, Eison AS, Mullins UL, Smith HL, Torrente JR, Wright RN, Yocca FD: Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry. 1995;56 Suppl 6:3-11. [PubMed:7649970]
  2. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Shin DS, Park MJ, Lee HA, Lee JY, Chung HC, Yoo DS, Chae CH, Park SJ, Kim KS, Bae MA: A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method. Toxicol Appl Pharmacol. 2014 Feb 1;274(3):361-71. doi: 10.1016/j.taap.2013.12.012. Epub 2013 Dec 26. [PubMed:24374264]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Flockhart Table - Indiana University [Link]
Details
2. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. [PubMed:9098663]
  2. DeVane CL, Donovan JL, Liston HL, Markowitz JS, Cheng KT, Risch SC, Willard L: Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004 Feb;24(1):4-10. [PubMed:14709940]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. von Moltke LL, Greenblatt DJ, Granda BW, Grassi JM, Schmider J, Harmatz JS, Shader RI: Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions. Psychopharmacology (Berl). 1999 Jul;145(1):113-22. [PubMed:10445380]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Not Available
Gene Name
CYP2B
Uniprot ID
Q14097
Uniprot Name
CYP2B protein
Molecular Weight
43147.81 Da
References
  1. Haduch A, Wojcikowski J, Daniel WA: Effect of selected antidepressant drugs on cytochrome P450 2B (CYP2B) in rat liver. An in vitro and in vivo study. Pharmacol Rep. 2008 Nov-Dec;60(6):957-65. [PubMed:19211989]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. von Moltke LL, Greenblatt DJ, Granda BW, Grassi JM, Schmider J, Harmatz JS, Shader RI: Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions. Psychopharmacology (Berl). 1999 Jul;145(1):113-22. [PubMed:10445380]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Greene DS, Barbhaiya RH: Clinical pharmacokinetics of nefazodone. Clin Pharmacokinet. 1997 Oct;33(4):260-75. doi: 10.2165/00003088-199733040-00002. [PubMed:9342502]
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Stormer E, von Moltke LL, Perloff MD, Greenblatt DJ: P-glycoprotein interactions of nefazodone and trazodone in cell culture. J Clin Pharmacol. 2001 Jul;41(7):708-14. [PubMed:11452702]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:38