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Identification
NameTrazodone
Accession NumberDB00656  (APRD00533)
TypeSmall Molecule
GroupsApproved, 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
SynonymLanguageCode
2-(3-[4-(3-Chlorophenyl)-1-piperazinyl]propyl)[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneNot AvailableNot Available
TrazodonaSpanishINN
TrazodoneNot AvailableNot Available
TrazodonumLatinINN
Salts
Name/CAS Structure Properties
Trazodone Hydrochloride
25332-39-2
Thumb
  • InChI Key: OHHDIOKRWWOXMT-UHFFFAOYSA-N
  • Monoisotopic Mass: 407.127965797
  • Average Mass: 408.325
DBSALT000344
Brand names
NameCompany
BeneficatNot Available
DepraxNot Available
DesirelNot Available
DesyrelBristol-Myers Squibb
Desyrel DividoseBristol-Myers Squibb
MesyrelNot Available
MolipaxinNot Available
OleptroNot Available
ThombranNot Available
TrazorelNot Available
TrialodineNot Available
TritticoNot Available
Brand mixturesNot Available
Categories
CAS number19794-93-5
WeightAverage: 371.864
Monoisotopic: 371.151288058
Chemical FormulaC19H22ClN5O
InChI KeyPHLBKPHSAVXXEF-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPiperazines
SubclassPhenylpiperazines
Direct parentPhenylpiperazines
Alternative parentsTriazolopyridines; Chlorobenzenes; Diazinanes; Pyridines and Derivatives; Aryl Chlorides; Triazoles; Tertiary Amines; Polyamines; Organochlorides
Substituentstriazolopyridine; chlorobenzene; aryl halide; aryl chloride; pyridine; benzene; 1,4-diazinane; triazole; azole; 1,2,4-triazole; tertiary amine; polyamine; amine; organochloride; organonitrogen compound; organohalogen
Classification descriptionThis compound belongs to the phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Pharmacology
IndicationFor the treatment of depression.
PharmacodynamicsTrazodone 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 actionTrazodone 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.
AbsorptionRapidly and almost completely absorbed following oral administration. Food may decrease the rate and extent of absorption.
Volume of distributionNot Available
Protein binding89-95% 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.

SubstrateEnzymesProduct
Trazodone
4'-hydroxytrazodone glutathione Details
Trazodone
m-chlorophenylpiperazine (m-CPP) Details
Trazodone
triazolopropionic acidDetails
Trazodone
triazolopyridinone epoxideDetails
Trazodone
4'-hydroxytrazodone Details
Trazodone
Not Available
GlutathioneDetails
Trazodone
Not Available
Glucuonic acidDetails
Trazodone
Not Available
Oxotriazolopyridinpropionic acidDetails
Route of eliminationNot Available
Half lifeUndergoes biphasic elimination with an initial phase t1/2 α of 3-6 hours and a terminal phase t1/2 β of 5-9 hours.
ClearanceNot Available
ToxicityLD50=96mg/kg (i.v. in mice)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9829
Caco-2 permeable - 0.6166
P-glycoprotein substrate Substrate 0.547
P-glycoprotein inhibitor I Inhibitor 0.8634
P-glycoprotein inhibitor II Inhibitor 0.8889
Renal organic cation transporter Inhibitor 0.6479
CYP450 2C9 substrate Non-substrate 0.7897
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.7408
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.6613
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.83
Ames test Non AMES toxic 0.5133
Carcinogenicity Non-carcinogens 0.8545
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.7007 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.8994
hERG inhibition (predictor II) Inhibitor 0.7503
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
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral150 mg
TabletOral300 mg
TabletOral50 mg
Prices
Unit descriptionCostUnit
Trazodone hcl powder8.26USDg
Desyrel 300 mg tablet6.03USDtablet
TraZODone HCl 300 mg tablet5.65USDtablet
Trazodone 300 mg tablet5.44USDtablet
Desyrel 100 mg tablet4.6USDtablet
Desyrel 150 mg tablet3.39USDtablet
TraZODone HCl 150 mg tablet1.53USDtablet
Trazodone 150 mg tablet1.47USDtablet
Desyrel 50 mg tablet1.33USDtablet
TraZODone HCl 100 mg tablet0.76USDtablet
Trazodone 100 mg tablet0.73USDtablet
Apo-Trazodone D 150 mg Tablet0.61USDtablet
Desyrel Dividose 150 mg Tablet0.61USDtablet
Novo-Trazodone 150 mg Tablet0.61USDtablet
Nu-Trazodone-D 150 mg Tablet0.61USDtablet
Ratio-Trazodone 150 mg Tablet0.61USDtablet
TraZODone HCl 50 mg tablet0.59USDtablet
Trazodone 50 mg tablet0.57USDtablet
Nu-Trazodone 100 mg Tablet0.41USDtablet
Pms-Trazodone 100 mg Tablet0.41USDtablet
Ratio-Trazodone 100 mg Tablet0.41USDtablet
Apo-Trazodone 100 mg Tablet0.41USDtablet
Desyrel 100 mg Tablet0.41USDtablet
Mylan-Trazodone 100 mg Tablet0.41USDtablet
Novo-Trazodone 100 mg Tablet0.41USDtablet
Pms-Trazodone 75 mg Tablet0.34USDtablet
Apo-Trazodone 50 mg Tablet0.23USDtablet
Mylan-Trazodone 50 mg Tablet0.23USDtablet
Novo-Trazodone 50 mg Tablet0.23USDtablet
Nu-Trazodone 50 mg Tablet0.23USDtablet
Pms-Trazodone 50 mg Tablet0.23USDtablet
Ratio-Trazodone 50 mg Tablet0.23USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States66077482000-06-292020-06-29
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point87 °CPhysProp
water solubilitySparigly solubleNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.29ALOGPS
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
Spectra
Spectra
References
Synthesis ReferenceNot Available
General Reference
  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
  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
  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
  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
  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
  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
  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
External Links
ResourceLink
KEGG CompoundC07156
PubChem Compound5533
PubChem Substance46506648
ChemSpider5332
ChEBI9654
ChEMBLCHEMBL621
Therapeutic Targets DatabaseDAP000104
PharmGKBPA451744
IUPHAR213
Guide to Pharmacology213
Drug Product Database2249804
RxListhttp://www.rxlist.com/cgi/generic/traz.htm
Drugs.comhttp://www.drugs.com/trazodone.html
WikipediaTrazodone
ATC CodesN06AX05
AHFS Codes
  • 28:16.04.24
PDB EntriesNot Available
FDA labelshow(151 KB)
MSDSshow(73.7 KB)
Interactions
Drug Interactions
Drug
AlmotriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AminoglutethimideThe CYP3A4 inducer, Aminoglutethimide, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Aminoglutethimide is initiated, discontinued or dose changed.
AmiodaroneThe CYP3A4 inhibitor, Amiodarone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amiodarone is initiated, discontinued or dose changed.
AmitriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AmoxapineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AmprenavirThe protease inhibitor, Amprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amprenavir is initiated, discontinued or dose changed.
AprepitantThe CYP3A4 inhibitor, Aprepitant, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Aprepitant is initiated, discontinued or dose changed.
AtazanavirThe protease inhibitor, Atazanavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Atazanavir is initiated, discontinued or dose changed.
BosentanThe CYP3A4 inducer, Bosentan, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Bosentan is initiated, discontinued or dose changed.
BromocriptineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
BuspironeIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
CabergolineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
CarbamazepineThe CYP3A4 inducer, Carbamazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Carbamazepine is initiated, discontinued or dose changed.
CimetidineThe CYP3A4 inhibitor, Cimetidine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Cimetidine is initiated, discontinued or dose changed.
CitalopramIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ClarithromycinThe CYP3A4 inhibitor, Clarithromycin, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Clarithromycin is initiated, discontinued or dose changed.
ClomipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ClotrimazoleThe CYP3A4 inhibitor, Clotrimazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Clotrimazole is initiated, discontinued or dose changed.
ConivaptanThe CYP3A4 inhibitor, Conivaptan, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Conivaptan is initiated, discontinued or dose changed.
CyclosporineThe CYP3A4 inhibitor, Cyclosporine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Cyclosporine is initiated, discontinued or dose changed.
Dabigatran etexilateP-Glycoprotein inducers such as trazodone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
DarunavirThe protease inhibitor, Darunavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Darunavir is initiated, discontinued or dose changed.
DelavirdineThe CYP3A4 inhibitor, Delavirdine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Delavirdine is initiated, discontinued or dose changed.
DesipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DexamethasoneThe CYP3A4 inducer, Dexamethasone, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Dexamethasone is initiated, discontinued or dose changed.
DextromethorphanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DihydroergotamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DiltiazemThe CYP3A4 inhibitor, Diltizem, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Diltiazem is initiated, discontinued or dose changed.
DonepezilPossible antagonism of action
DoxepinIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DuloxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EfavirenzThe CYP3A4 inhibitor and inducer, Efavirenz, may alter Trazodone efficacy/toxicity by altering Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Efavirenz is initiated, discontinued or dose changed.
EletriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ergoloid mesylateIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ErgonovineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ErgotamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ErythromycinThe CYP3A4 inhibitor, Erythromycin , may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Erythromycin is initiated, discontinued or dose changed.
EscitalopramIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EtravirineThe CYP3A4 inducer, Etravirene, may decrease Trazodone efficacy/toxicity by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Etravirine is initiated, discontinued or dose changed.
FluconazoleThe CYP3A4 inhibitor, Fluconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fluconazole is initiated, discontinued or dose changed.
FluoxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FluvoxamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FosamprenavirThe protease inhibitor, Fosamprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fosamprenavir is initiated, discontinued or dose changed.
FosphenytoinThe CYP3A4 inducer, Fosphenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fosphenytoin is initiated, discontinued or dose changed.
FrovatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FurazolidoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
GalantaminePossible antagonism of action
Ginkgo bilobaIncreased effect and toxicity of both agents
HaloperidolThe CYP3A4 inhibitor, Haloperidol, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. The CYP2D6 inhibitor, Trazodone, may increase the efficacy of Haloperidol by decreasing Haloperidol metabolism and clearance. Monitor for changes in Trazodone and Haloperidol efficacy/toxicity if either agent is initiated, discontinued or dose changed.
ImatinibThe CYP3A4 inhibitor, Imatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Imatinib is initiated, discontinued or dose changed.
ImipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
IndinavirThe protease inhibitor, Indinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism via CYP3A4. Monitor for changes in Trazodone efficacy/toxicity if Indinavir is initiated, discontinued or dose changed.
IsocarboxazidIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
IsoniazidThe CYP3A4 inhibitor, Isoniazid, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Isoniazid is initiated, discontinued or dose changed.
ItraconazoleThe CYP3A4 inhibitor, Itraconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Itraconazole is initiated, discontinued or dose changed.
KetoconazoleThe CYP3A4 inhibitor, Ketoconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Ketoconazole is initiated, discontinued or dose changed.
LapatinibThe CYP3A4 inhibitor, Lapatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lapatinib is initiated, discontinued or dose changed.
LidocaineThe CYP3A4 inhibitor, Lidocaine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lidocaine is initiated, discontinued or dose changed.
LinezolidIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
LithiumIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
LopinavirThe protease inhibitor, Lopinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lopinavir is initiated, discontinued or dose changed.
MaprotilineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MethylergometrineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MetronidazoleThe CYP3A4 inhibitor, Metronidazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Metronidazole is initiated, discontinued or dose changed.
MiconazoleThe CYP3A4 inhibitor, Miconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Miconazole is initiated, discontinued or dose changed.
MirtazapineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MoclobemideIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
NafcillinThe CYP3A4 inducer, Nafcillin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Nafcillin is initiated, discontinued or dose changed.
NaratriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
NefazodoneIncreased 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.
NelfinavirThe protease inhibitor, Nelfinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Nelfinavir is initiated, discontinued or dose changed.
NevirapineThe CYP3A4 inducer, Nevirapine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Nevirapine is initiated, discontinued or dose changed.
NicardipineThe CYP3A4 inhibitor, Nicardipine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Nicardipine is initiated, discontinued or dose changed.
NorfloxacinThe CYP3A4 inhibitor, Norfloxacin, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Norfloxacin is initiated, discontinued or dose changed.
NortriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
OxcarbazepineThe CYP3A4 inducer, Oxcarbazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Oxcarbazepine is initiated, discontinued or dose changed.
ParoxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PentobarbitalThe CYP3A4 inducer, Pentobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Pentobarbital is initiated, discontinued or dose changed.
PergolideIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PethidineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PhenelzineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PhenobarbitalThe CYP3A4 inducer, Phenobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenobarbital is initiated, discontinued or dose changed.
PhenytoinThe CYP3A4 inducer, Phenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenytoin is initiated, discontinued or dose changed.
PosaconazoleThe CYP3A4 inhibitor, Posaconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Posaconazole is initiated, discontinued or dose changed.
PrimidoneThe CYP3A4 inducer, Primidone, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Primidone is initiated, discontinued or dose changed.
ProcarbazineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PromethazineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ProtriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
QuinidineThe CYP3A4 inhibitor, Quinidine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Quinidine is initiated, discontinued or dose changed.
RasagilineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
RifabutinThe CYP3A4 inducer, Rifabutin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifabutin is initiated, discontinued or dose changed.
RifampicinThe CYP3A4 inducer, Rifampin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifampin is initiated, discontinued or dose changed.
RifapentineThe CYP3A4 inducer, Rifapentine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifapentine is initiated, discontinued or dose changed.
RitonavirThe protease inhibitor, Ritonavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Ritonavir is initiated, discontinued or dose changed.
RivastigminePossible antagonism of action
RizatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
S-AdenosylmethionineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SaquinavirThe protease inhibitor, Saquinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Saquinavir is initiated, discontinued or dose changed.
SelegilineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SertralineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SibutramineIncreased risk of serotonin syndrome. Avoid concomitant therapy.
SitaxentanThe CYP3A4 inhibitor, Sitaxsenten, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Norfloxacin is initiated, discontinued or dose changed.
St. John's WortIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SumatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TamoxifenTrazodone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
TamsulosinTrazodone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Trazodone is initiated, discontinued, or dose changed.
TelithromycinThe CYP3A4 inhibitor, Telithromycin, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Telithromycin is initiated, discontinued or dose changed.
TetracyclineThe CYP3A4 inhibitor, Tetracycline, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Tetracycline is initiated, discontinued or dose changed.
TipranavirThe protease inhibitor, Tipranavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Tipranavir is initiated, discontinued or dose changed.
TramadolThe use of two serotonin modulators, such as trazodone and tramadol, may increase the risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TranylcypromineIncreased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TriprolidineThe CNS depressants, Triprolidine and Trazodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VerapamilThe CYP3A4 inhibitor, Verapamil, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Verapamil is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of trazodone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trazodone if voriconazole is initiated, discontinued or dose changed.
ZolmitriptanUse of two serotonin modulators, such as zolmitriptan and trazodone, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Food decreases the rate and extent of absorption.

Targets

1. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

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
  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
  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
  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
  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
  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

2. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

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
  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

3. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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

4. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: partial agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

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
  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
  3. Subhash MN, Srinivas BN, Vinod KY: Alterations in 5-HT receptors and adenylyl cyclase response by trazodone in regions of rat brain. Life Sci. 2002 Aug 16;71(13):1559-67. Pubmed

5. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

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

6. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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

7. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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
  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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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
  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
  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

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

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

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

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

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2008 Jan 31. 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

Carriers

1. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11