Identification

Name
Trazodone
Accession Number
DB00656  (APRD00533)
Type
Small Molecule
Groups
Approved, Investigational
Description

A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309)

Structure
Thumb
Synonyms
  • 2-(3-[4-(3-chlorophenyl)-1-piperazinyl]propyl)[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one
  • Trazodona
  • Trazodone
  • Trazodonum
External IDs
J10.767K
Product Ingredients
IngredientUNIICASInChI Key
Trazodone hydrochloride6E8ZO8LRNM25332-39-2OHHDIOKRWWOXMT-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DesyrelTablet300 mg/1OralBristol Myers Squibb2007-01-012008-11-30Us
DesyrelTablet150 mg/1OralBristol Myers Squibb2007-01-012008-06-30Us
DesyrelTablet150 mg/1OralPhysicians Total Care, Inc.2007-01-012011-05-31Us
Desyrel Dividose Tab 300mgTablet300 mgOralBristol Labs Division Of Bristol Myers Squibb1989-12-311999-08-09Canada
Desyrel Dividose Tablet 150 mgTablet150 mgOralBristol Myers Squibb1988-12-312010-01-05Canada
Desyrel Tab 100mgTablet100 mgOralBristol Myers Squibb1983-12-312010-09-07Canada
Desyrel Tab 50mgTablet50 mgOralBristol Myers Squibb1983-12-312010-05-14Canada
OleptroTablet, extended release150 mg/1OralAngelini Pharma Inc.2010-02-022016-02-29Us
OleptroTablet, extended release300 mgOralAngelini Pharma Inc.2011-03-09Not applicableCanada
OleptroTablet, extended release300 mg/1OralAngelini Pharma Inc.2010-02-022016-02-29Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-trazodone D Tablets 150mgTablet150 mgOralApotex Corporation1995-12-31Not applicableCanada
Apo-trazodone Tablets 100mgTablet100 mgOralApotex Corporation1995-12-31Not applicableCanada
Apo-trazodone Tablets 50mgTablet50 mgOralApotex Corporation1995-12-31Not applicableCanada
Dom-trazodone Tablets - 50mgTablet50 mgOralDominion Pharmacal1996-12-31Not applicableCanada
Dom-trazodone Tablets-100mgTablet100 mgOralDominion Pharmacal1996-12-31Not applicableCanada
Mar-trazodoneTablet150 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-trazodoneTablet50 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-trazodoneTablet100 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mylan-trazodoneTablet100 mgOralMylan Pharmaceuticals1997-09-052016-06-28Canada
Mylan-trazodoneTablet50 mgOralMylan Pharmaceuticals1997-09-052016-06-28Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
TrazamineTrazodone hydrochloride (50 mg/1) + Choline (250 mg/1)KitPhysician Therapeutics Llc2011-02-03Not applicableUs
International/Other Brands
Beneficat / Deprax / Desirel / Desyrel (Bristol-Myers Squibb) / Desyrel Dividose (Bristol-Myers Squibb) / Mesyrel / Molipaxin / Thombran / Trialodine / Trittico
Categories
UNII
YBK48BXK30
CAS number
19794-93-5
Weight
Average: 371.864
Monoisotopic: 371.151288058
Chemical Formula
C19H22ClN5O
InChI Key
PHLBKPHSAVXXEF-UHFFFAOYSA-N
InChI
InChI=1S/C19H22ClN5O/c20-16-5-3-6-17(15-16)23-13-11-22(12-14-23)8-4-10-25-19(26)24-9-2-1-7-18(24)21-25/h1-3,5-7,9,15H,4,8,10-14H2
IUPAC Name
2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-3-one
SMILES
ClC1=CC=CC(=C1)N1CCN(CCCN2N=C3C=CC=CN3C2=O)CC1

Pharmacology

Indication

For the treatment of depression.

Associated Conditions
Pharmacodynamics

Trazodone is an antidepressant and hypnotic chemically unrelated to tricyclic, tetracyclic, or other known antidepressant agents. The mechanism of trazodone's antidepressant action in man is not fully understood. In animals, trazodone selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor, 5-hydroxytryptophan. Cardiac conduction effects of trazodone in the anesthetized dog are qualitatively dissimilar and quantitatively less pronounced than those seen with tricyclic antidepressants. Trazodone is not a monoamine oxidase inhibitor and, unlike amphetamine-type drugs, does not stimulate the central nervous system. In man, trazodone is well absorbed after oral administration without selective localization in any tissue. Since the clearance of trazodone from the body is sufficiently variable, in some patients trazodone may accumulate in the plasma.

Mechanism of action

Trazodone binds at 5-HT2 receptor, it acts as a serotonin agonist at high doses and a serotonin antagonist at low doses. Like fluoxetine, trazodone's antidepressant activity likely results from blockage of serotonin reuptake by inhibiting serotonin reuptake pump at the presynaptic neuronal membrane. If used for long time periods, postsynaptic neuronal receptor binding sites may also be affected. The sedative effect of trazodone is likely the result of alpha-adrenergic blocking action and modest histamine blockade at H1 receptor. It weakly blocks presynaptic alpha2-adrenergic receptors and strongly inhibits postsynaptic alpha1 receptors. Trazodone does not affect the reuptake of norepinephrine or dopamine within the CNS.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Human
A5-hydroxytryptamine receptor 2C
agonist
Human
ASodium-dependent serotonin transporter
inhibitor
Human
A5-hydroxytryptamine receptor 1A
partial agonist
Human
UHistamine H1 receptor
antagonist
Human
NAlpha-1A adrenergic receptor
antagonist
Human
NAlpha-2A adrenergic receptor
antagonist
Human
Absorption

Rapidly and almost completely absorbed following oral administration. Food may decrease the rate and extent of absorption.

Volume of distribution
Not Available
Protein binding

89-95% bound to plasma proteins in vitro

Metabolism

Undergoes extensive hepatic metabolism via hydroxylation, N-dealkylation, N-oxidation and splitting of the pyridine ring. Cytochrome P450 (CYP) 3A4 catalyzes the formation of the major active metabolite, m-chlorophenylpiperazine (m-CPP). Metabolites may be further conjugated to glucuonic acid or glutathione. CYP2D6 is responsible for 4'-hydroxylation of m-CPP and the formation of at least one glutathione conjugates of m-CPP, a quinone imine-sulhydryl adduct. Oxotriazolopyridinpropionic acid, an inactive metabolite, and its conjugates account for about 20% of the total excreted oral dose. Less than 1% of the oral dose is excreted unchanged. Approximately 70-75% of the dose is eliminated in urine with the remainder being excreted in feces via biliary elimination.

Route of elimination
Not Available
Half life

Undergoes biphasic elimination with an initial phase t1/2 α of 3-6 hours and a terminal phase t1/2 β of 5-9 hours.

Clearance
Not Available
Toxicity

LD50=96mg/kg (i.v. in mice)

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinTrazodone may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinTrazodone may decrease the anticoagulant activities of (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when Trazodone is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Trazodone is combined with 1-benzylimidazole.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Trazodone is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Trazodone 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 Trazodone.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Trazodone.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Trazodone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Trazodone.
Food Interactions
  • Avoid alcohol.
  • Food decreases the rate and extent of absorption.

References

General References
  1. Marek GJ, McDougle CJ, Price LH, Seiden LS: A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action. Psychopharmacology (Berl). 1992;109(1-2):2-11. [PubMed:1365657]
  2. Jauch R, Kopitar Z, Prox A, Zimmer A: [Pharmacokinetics and metabolism of trazodone in man (author's transl)]. Arzneimittelforschung. 1976;26(11):2084-9. [PubMed:1037253]
  3. Rotzinger S, Fang J, Baker GB: Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998 Jun;26(6):572-5. [PubMed:9616194]
  4. Kalgutkar AS, Henne KR, Lame ME, Vaz AD, Collin C, Soglia JR, Zhao SX, Hop CE: Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005 Jun 30;155(1-2):10-20. Epub 2005 Apr 18. [PubMed:15978881]
  5. Otani K, Yasui N, Kaneko S, Ishida M, Ohkubo T, Osanai T, Sugawara K, Fukushima Y: Trazodone treatment increases plasma prolactin concentrations in depressed patients. Int Clin Psychopharmacol. 1995 Jun;10(2):115-7. [PubMed:7673654]
  6. Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Gruber G, Mandl M, Strobl R, Gollner D, Prause W, Saletu B: Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):249-60. [PubMed:11817501]
  7. Fink HA, MacDonald R, Rutks IR, Wilt TJ: Trazodone for erectile dysfunction: a systematic review and meta-analysis. BJU Int. 2003 Sep;92(4):441-6. [PubMed:12930437]
External Links
Human Metabolome Database
HMDB0014794
KEGG Drug
D08626
KEGG Compound
C07156
PubChem Compound
5533
PubChem Substance
46506648
ChemSpider
5332
BindingDB
50073444
ChEBI
9654
ChEMBL
CHEMBL621
Therapeutic Targets Database
DAP000104
PharmGKB
PA451744
IUPHAR
213
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Trazodone
ATC Codes
N06AX05 — Trazodone
AHFS Codes
  • 28:16.04.24 — Serotonin Modulators
FDA label
Download (151 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0SuspendedBasic ScienceSleep Apnea, Obstructive; Post-Traumatic Stress Disorders1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentBioavailability / Healthy Volunteers / Pharmacokinetics1
1CompletedTreatmentDepression1
1CompletedTreatmentHealthy Volunteers3
1RecruitingTreatmentSleep Apnea, Obstructive1
1Unknown StatusTreatmentHealthy Volunteers1
2CompletedTreatmentAlcohol Dependence1
2CompletedTreatmentPainful Diabetic Neuropathy (PDN)1
2Not Yet RecruitingTreatmentPainful Diabetic Neuropathy (PDN)1
2RecruitingBasic ScienceSleep Disordered Breathing (SDB) / Spinal Cord Injuries (SCI)1
2, 3CompletedTreatmentDepression1
3CompletedTreatmentAlzheimer's Disease (AD)1
3CompletedTreatmentAlzheimer's Disease (AD) / Sleep / Sleep disorders and disturbances / Sleeplessness1
3CompletedTreatmentMajor Depressive Disorder (MDD)2
3CompletedTreatmentOpiate Addiction / Poor Quality Sleep1
3CompletedTreatmentSleep Disorder1
3Not Yet RecruitingTreatmentSleeplessness1
3RecruitingTreatmentEnd Stage Renal Disease (ESRD) / Sleeplessness1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4Active Not RecruitingTreatmentInsomnia Comorbid to Psychiatric Disorder / Primary Insomnia1
4CompletedPreventionAcellular Pertussis / Diphtheria / Healthy Volunteers / Tetanus1
4CompletedTreatmentFibromyalgia1
4CompletedTreatmentSchizophrenic Disorders1
4Not Yet RecruitingTreatmentPain, Chronic / Sleep Bruxism / Sleep Disorder / TMD / TMJ Pain1
4RecruitingOtherSleep Apnea Syndrome / Spinal Cord Injuries (SCI)1
4TerminatedTreatmentAcute Agitation / Delirium1
4TerminatedTreatmentMental Health Disorder / Sleeplessness / Substance Use Disorder (SUD)1
4Unknown StatusTreatmentMajor Depressive Disorder (MDD)1
Not AvailableActive Not RecruitingTreatmentSleeplessness1
Not AvailableCompletedBasic ScienceSleep Apnea, Obstructive1
Not AvailableCompletedTreatmentSexual Dysfunctions1
Not AvailableCompletedTreatmentSpinal Stenosis of Lumbar Region1
Not AvailableRecruitingTreatmentAlcohol-Related Disorders / Brain Injury / Depression / Disease, Chronic / Mild Cognitive Impairment (MCI) / Pain NOS / Posttraumatic Stress Disorders / Quality of Life / Substance-Related Disorders / Suicidal Thoughts / Wounds and Injuries1
Not AvailableRecruitingTreatmentAntidepressant Drug Adverse Reaction / Depression1
Not AvailableUnknown StatusTreatmentTreatment Resistant Depression (TRD)1

Pharmacoeconomics

Manufacturers
  • Labopharm inc
  • Apothecon inc div bristol myers squibb
  • Alvogen inc
  • American therapeutics inc
  • Apotex inc
  • Matrix laboratories ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Quantum pharmics ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Apothecon
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Barr Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Golden State Medical Supply Inc.
  • Goldline Laboratories Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Labopharm Inc.
  • Lake Erie Medical and Surgical Supply
  • Letco Medical Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Neighborcare Repackaging Inc.
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharma Pac LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Shanghai World Prospect Industrial Co. Ltd.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral150 mg
TabletOral50 mg
TabletOral300 mg/1
TabletOral300 mg
Tablet, extended releaseOral150 mg/1
Tablet, extended releaseOral150 mg
Tablet, extended releaseOral300 mg
Tablet, extended releaseOral300 mg/1
TabletOral100 mg
TabletOral75 mg
Kit
TabletOral100 mg/1
TabletOral100 mg/301
TabletOral150 mg/1
TabletOral50 mg/301
TabletOral50 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral50 mg/1
TabletOral68.25 mg
Prices
Unit descriptionCostUnit
Trazodone hcl powder8.26USD g
Desyrel 300 mg tablet6.03USD tablet
TraZODone HCl 300 mg tablet5.65USD tablet
Trazodone 300 mg tablet5.44USD tablet
Desyrel 100 mg tablet4.6USD tablet
Desyrel 150 mg tablet3.39USD tablet
TraZODone HCl 150 mg tablet1.53USD tablet
Trazodone 150 mg tablet1.47USD tablet
Desyrel 50 mg tablet1.33USD tablet
TraZODone HCl 100 mg tablet0.76USD tablet
Trazodone 100 mg tablet0.73USD tablet
Apo-Trazodone D 150 mg Tablet0.61USD tablet
Desyrel Dividose 150 mg Tablet0.61USD tablet
Novo-Trazodone 150 mg Tablet0.61USD tablet
Nu-Trazodone-D 150 mg Tablet0.61USD tablet
Ratio-Trazodone 150 mg Tablet0.61USD tablet
TraZODone HCl 50 mg tablet0.59USD tablet
Trazodone 50 mg tablet0.57USD tablet
Nu-Trazodone 100 mg Tablet0.41USD tablet
Pms-Trazodone 100 mg Tablet0.41USD tablet
Ratio-Trazodone 100 mg Tablet0.41USD tablet
Apo-Trazodone 100 mg Tablet0.41USD tablet
Desyrel 100 mg Tablet0.41USD tablet
Mylan-Trazodone 100 mg Tablet0.41USD tablet
Novo-Trazodone 100 mg Tablet0.41USD tablet
Pms-Trazodone 75 mg Tablet0.34USD tablet
Apo-Trazodone 50 mg Tablet0.23USD tablet
Mylan-Trazodone 50 mg Tablet0.23USD tablet
Novo-Trazodone 50 mg Tablet0.23USD tablet
Nu-Trazodone 50 mg Tablet0.23USD tablet
Pms-Trazodone 50 mg Tablet0.23USD tablet
Ratio-Trazodone 50 mg Tablet0.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8133893No2012-03-132029-03-13Us
US6607748No2003-08-192020-06-29Us
US7829120No2010-11-092027-03-27Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)87 °CPhysProp
water solubilitySparigly solubleNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.29 mg/mLALOGPS
logP2.68ALOGPS
logP3.13ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)7.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area42.39 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity105.88 m3·mol-1ChemAxon
Polarizability40.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9829
Caco-2 permeable-0.6166
P-glycoprotein substrateSubstrate0.547
P-glycoprotein inhibitor IInhibitor0.8634
P-glycoprotein inhibitor IIInhibitor0.8889
Renal organic cation transporterInhibitor0.6479
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.6613
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.83
Ames testNon AMES toxic0.5133
CarcinogenicityNon-carcinogens0.8545
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7007 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8994
hERG inhibition (predictor II)Inhibitor0.7503
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)MSsplash10-0a4i-7980000000-5d2bde624fdd9a946993
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-0609000000-cee74b5bf3182c2aa324

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 / Aryl 1,2,4-triazolones / Triazolopyridines / Aniline and substituted anilines / Dialkylarylamines / Pyridinones / Chlorobenzenes / N-alkylpiperazines / Aryl chlorides / Heteroaromatic compounds
show 7 more
Substituents
Phenylpiperazine / N-arylpiperazine / Aryl 1,2,4-triazol-3-one / Triazolopyridine / Tertiary aliphatic/aromatic amine / Aniline or substituted anilines / Dialkylarylamine / Pyridinone / Chlorobenzene / N-alkylpiperazine
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monochlorobenzenes, N-alkylpiperazine, triazolopyridine (CHEBI:9654)

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. Pazzagli M, Giovannini MG, Pepeu G: Trazodone increases extracellular serotonin levels in the frontal cortex of rats. Eur J Pharmacol. 1999 Nov 3;383(3):249-57. [PubMed:10594316]
  2. Marcoli M, Rosu C, Bonfanti A, Raiteri M, Maura G: Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers. J Pharmacol Exp Ther. 2001 Dec;299(3):1106-11. [PubMed:11714900]
  3. Marek GJ, McDougle CJ, Price LH, Seiden LS: A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action. Psychopharmacology (Berl). 1992;109(1-2):2-11. [PubMed:1365657]
  4. Luparini MR, Garrone B, Pazzagli M, Pinza M, Pepeu G: A cortical GABA-5HT interaction in the mechanism of action of the antidepressant trazodone. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Nov;28(7):1117-27. [PubMed:15610924]
  5. Conn PJ, Sanders-Bush E: Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors. J Pharmacol Exp Ther. 1987 Aug;242(2):552-7. [PubMed:3039120]
  6. 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
Agonist
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. Fiorella D, Rabin RA, Winter JC: The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of m-chlorophenylpiperazine. Psychopharmacology (Berl). 1995 May;119(2):222-30. [PubMed:7659770]
  2. Conn PJ, Sanders-Bush E: Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors. J Pharmacol Exp Ther. 1987 Aug;242(2):552-7. [PubMed:3039120]
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. 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
Yes
Actions
Partial agonist
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. Odagaki Y, Toyoshima R, Yamauchi T: Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding. J Psychopharmacol. 2005 May;19(3):235-41. [PubMed:15888508]
  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]
  3. Subhash MN, Srinivas BN, Vinod KY: Alterations in 5-HT(1A) receptors and adenylyl cyclase response by trazodone in regions of rat brain. Life Sci. 2002 Aug 16;71(13):1559-67. [PubMed:12127910]
Details
5. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 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. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
  3. Noguchi S, Inukai T, Kuno T, Tanaka C: The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking. Physiol Behav. 1992 Jun;51(6):1123-7. [PubMed:1353628]
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. 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
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]
  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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Rotzinger S, Fang J, Baker GB: Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998 Jun;26(6):572-5. [PubMed:9616194]
  2. Kalgutkar AS, Henne KR, Lame ME, Vaz AD, Collin C, Soglia JR, Zhao SX, Hop CE: Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005 Jun 30;155(1-2):10-20. Epub 2005 Apr 18. [PubMed:15978881]
  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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Wen B, Ma L, Rodrigues AD, Zhu M: Detection of novel reactive metabolites of trazodone: evidence for CYP2D6-mediated bioactivation of m-chlorophenylpiperazine. Drug Metab Dispos. 2008 May;36(5):841-50. doi: 10.1124/dmd.107.019471. Epub 2008 Jan 31. [PubMed:18238857]
  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]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. [PubMed:2870173]

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]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 03:11