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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Groups approved, withdrawn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. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Nefazodona [Spanish]
Nefazodone Hcl
Nefazodone Hydrochloride
Nefazodonum [Latin]
Salts Not Available
Brand names
Name Company
Dutonin
Serzone
Brand mixtures Not Available
Categories
  • Antidepressants
  • Analgesics
  • Antidepressive Agents, Second-Generation
  • Serotonin Agents
CAS number 83366-66-9
Weight Average: 470.007
Monoisotopic: 469.224453
Chemical Formula C25H32ClN5O2
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Phenols and Derivatives
  • Ethers
  • Halobenzenes
  • Anisoles
  • Phenyl Esters
  • Anilines
Substructures
  • Triazoles
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Imines
  • Cyanamides
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the treatment of depression.
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.
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
Pharmacoeconomics
Manufacturers
  • Dr reddys laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
Form Route Strength
Tablet Oral 100 mg
Tablet Oral 150 mg
Tablet Oral 200 mg
Tablet Oral 250 mg
Tablet Oral 50 mg
Prices
Unit description Cost Unit
Nefazodone hcl 250 mg tablet 1.82 USD tablet
Nefazodone hcl 200 mg tablet 1.78 USD tablet
Nefazodone hcl 150 mg tablet 1.75 USD tablet
Nefazodone hcl 100 mg tablet 1.72 USD tablet
Nefazodone hcl 50 mg tablet 1.68 USD tablet
Serzone 100 mg tablet 1.53 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 83.5 °C PhysProp
logP 4.7 Not Available
Predicted Properties
Property Value Source
water solubility 6.98e-02 g/l ALOGPS
logP 3.71 ALOGPS
logP 4.65 ChemAxon
logS -3.8 ALOGPS
pKa (strongest basic) 7.09 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 51.62 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 132.38 ChemAxon
polarizability 51.85 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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
External Links
Resource Link
KEGG Compound C07256 Link_out
PubChem Compound 4449 Link_out
PubChem Substance 46508323 Link_out
ChemSpider 4294 Link_out
ChEBI 7494 Link_out
ChEMBL 7494 Link_out
Therapeutic Targets Database DAP000042 Link_out
PharmGKB PA450603 Link_out
Drug Product Database 2242822 Link_out
RxList http://www.rxlist.com/cgi/generic/nefaz.htm Link_out
Drugs.com http://www.drugs.com/cdi/nefazodone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Nefazodone Link_out
ATC Codes
  • N06AX06
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (152 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Almotriptan Increased risk of CNS adverse effects
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nefazodone is initiated, discontinued or dose changed.
Bromazepam Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if nefazodone is initiated, discontinued or dose changed. Dosage adjustments may be required.
Buspirone Nefazodone increases the effect of buspirone
Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
Carbamazepine Nefazodone increases the effect of carbamazepine
Cerivastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if nefazodone is initiated, discontinued or dose changed.
Cilostazol Nefazodone increases the effect of cilostazol
Cisapride Nefazodone increases serum levels of cisapride
Cyclosporine The antidepressant increases the effect and toxicity of cyclosporine
Dabigatran etexilate P-Glycoprotein inducers such as nefazodone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
Dantrolene Nefazodone may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nefazodone is initiated, discontinued or dose changed.
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroergotamine Possible ergotism and severe ischemia with this combination
Dronedarone Nefazodone is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
Eletriptan Increased risk of CNS adverse effects
Eplerenone Nefazodone increases the effect and toxicity of eplerenone
Ergotamine Possible ergotism and severe ischemia with this combination
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Frovatriptan Increased risk of CNS adverse effects
Isocarboxazid Possible severe adverse reaction with this combination
Linezolid Combination associated with possible serotoninergic syndrome
Loratadine Increased risk of cardiotoxicity
Lovastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if nefazodone is initiated, discontinued or dose changed.
Naratriptan Increased risk of CNS adverse effects
Pazopanib Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
Phenelzine Possible severe adverse reaction with this combination
Pimozide Nefazodone may increase the effect and toxicity of pimozide.
Rasagiline Possible severe adverse reaction with this combination
Rizatriptan Increased risk of CNS adverse effects
Saxagliptin Nefazodone is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
Sibutramine Risk of serotoninergic syndrome
Simvastatin Nefazodone may increase the effect and toxicity of simvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nefazodone is initiated, discontinued or dose changed.
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
St. John's Wort St. John's Wort increases the effect and toxicity of the SSRI, nefazodone.
Sumatriptan Increased risk of CNS adverse effects
Sunitinib Possible increase in sunitinib levels
Tacrolimus Nefazodone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nefazodone therapy is initiated, discontinued or altered.
Tadalafil Nefazodone may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Nefazodone may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Tamsulosin Nefazodone, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nefazodone is initiated, discontinued, or dose changed.
Telithromycin Co-administration may result in altered plasma concentrations of Nefazodone and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
Temsirolimus Nefazodone may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nefazodone is initiated, discontinued or dose changed.
Terbinafine Terbinafine may reduce the metabolism and clearance of Nefazodone. Consider alternate therapy or monitor for therapeutic/adverse effects of Nefazodone if Terbinafine is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tiagabine The strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nefazodone is initiated, discontinued or dose changed.
Tolterodine Nefazodone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Nefazodone is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
Tramadol Nefazodone may increase tramadol toxicity by decreasing tramadol metabolism and clearance. Increased risk of serotonin syndrome. Monitor for tramadol toxicity and symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. The CYP3A4 inhibitor, Nefazodone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for symtpoms of sertonin syndrome and changes in Trazodone efficacy/toxicity if Nefazodone is initiated, discontinued or dose changed.
Triazolam Nefazodone increases the effect of triazolam
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Nefazodone, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nefazodone is initiated, discontinued or dose changed.
Triprolidine The CNS depressants, Triprolidine and Nefazodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Vardenafil Nefazodone, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Verapamil Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nefazodone is initiated, discontinued or dose changed.
Vinblastine Nefazodone, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nefazodone is initiated, discontinued or dose changed.
Vincristine Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nefazodone is initiated, discontinued or dose changed.
Vinorelbine Nafazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nefazodone is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nefazodone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nefazodone if voriconazole is initiated, discontinued or dose changed.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and nafazodone, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Zolpidem Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if nefazodone is initiated, discontinued or dose changed.
Zonisamide Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nefazodone is initiated, discontinued or dose changed.
Zopiclone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nefazodone is initiated, discontinued or dose changed.
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.
Targets

1. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Horton JC, Trobe JD: Akinetopsia from nefazodone toxicity. Am J Ophthalmol. 1999 Oct;128(4):530-1. Pubmed
  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
  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
  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
  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
  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

2. 5-hydroxytryptamine 2C receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

4. 5-hydroxytryptamine 1A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Sodium-dependent noradrenaline transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

6. Sodium-dependent dopamine transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

7. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: other/unknown

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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

8. Alpha-2A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

9. Alpha-1A adrenergic receptor

Pharmacological action: no
Actions: antagonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Enzymes

1. Cytochrome P450 3A5

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A7

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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. Epub 2009 Nov 24. Pubmed
  5. 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

4. CYP2B protein

Actions: inhibitor
UniProt ID: Q14097 Link_out
Gene: CYP2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Cytochrome P450 2D6

Actions: substrate, inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19