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Identification
Name Trazodone
Accession Number DB00656 (APRD00533)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Trazodona [INN-Spanish]
Trazodone Hcl
Trazodone Hydrochloride
Trazodonum [INN-Latin]
Salts Not Available
Brand names
Name Company
Beneficat
Bimaran
Desirel
Desyrel Bristol-Myers Squibb
Desyrel Dividose Bristol-Myers Squibb
Molipaxin
Pragmazone
Sideril
Thombran
Tombran
Trazalon
Trazodil
Trazodon
Trazolan
Trazonil
Trialodine
Trittico
First Prev Next Last
Brand mixtures Not Available
Categories
  • Anti-anxiety Agents
  • Antidepressants, Second-Generation
  • Serotonin Uptake Inhibitors
  • Antidepressive Agents, Second-Generation
CAS number 19794-93-5
Weight Average: 371.864
Monoisotopic: 371.151288058
Chemical Formula C19H22ClN5O
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Triazolopyridines
Substructures
  • Triazoles
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Triazolopyridines
  • Piperazines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Pyridines
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
  • Anilines
Pharmacology
Indication For the treatment of depression.
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.
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Trazodone
4'-hydroxytrazodone glutathione Details
Trazodone
m-chlorophenylpiperazine (m-CPP) Details
Trazodone
triazolopropionic acid Details
Trazodone
triazolopyridinone epoxide Details
Trazodone
4'-hydroxytrazodone Details
Trazodone
    		Glutathione Details
    Trazodone
      		Glucuonic acid Details
      Trazodone
        		Oxotriazolopyridinpropionic acid Details
        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
        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
        Form Route Strength
        Tablet Oral 100 mg
        Tablet Oral 150 mg
        Tablet Oral 300 mg
        Tablet Oral 50 mg
        Prices
        Unit description Cost Unit
        Trazodone hcl powder 8.26 USD g
        Desyrel 300 mg tablet 6.03 USD tablet
        TraZODone HCl 300 mg tablet 5.65 USD tablet
        Trazodone 300 mg tablet 5.44 USD tablet
        Desyrel 100 mg tablet 4.6 USD tablet
        Desyrel 150 mg tablet 3.39 USD tablet
        TraZODone HCl 150 mg tablet 1.53 USD tablet
        Trazodone 150 mg tablet 1.47 USD tablet
        Desyrel 50 mg tablet 1.33 USD tablet
        TraZODone HCl 100 mg tablet 0.76 USD tablet
        Trazodone 100 mg tablet 0.73 USD tablet
        Apo-Trazodone D 150 mg Tablet 0.61 USD tablet
        Desyrel Dividose 150 mg Tablet 0.61 USD tablet
        Novo-Trazodone 150 mg Tablet 0.61 USD tablet
        Nu-Trazodone-D 150 mg Tablet 0.61 USD tablet
        Ratio-Trazodone 150 mg Tablet 0.61 USD tablet
        TraZODone HCl 50 mg tablet 0.59 USD tablet
        Trazodone 50 mg tablet 0.57 USD tablet
        Nu-Trazodone 100 mg Tablet 0.41 USD tablet
        Pms-Trazodone 100 mg Tablet 0.41 USD tablet
        Ratio-Trazodone 100 mg Tablet 0.41 USD tablet
        Apo-Trazodone 100 mg Tablet 0.41 USD tablet
        Desyrel 100 mg Tablet 0.41 USD tablet
        Mylan-Trazodone 100 mg Tablet 0.41 USD tablet
        Novo-Trazodone 100 mg Tablet 0.41 USD tablet
        Pms-Trazodone 75 mg Tablet 0.34 USD tablet
        Apo-Trazodone 50 mg Tablet 0.23 USD tablet
        Mylan-Trazodone 50 mg Tablet 0.23 USD tablet
        Novo-Trazodone 50 mg Tablet 0.23 USD tablet
        Nu-Trazodone 50 mg Tablet 0.23 USD tablet
        Pms-Trazodone 50 mg Tablet 0.23 USD tablet
        Ratio-Trazodone 50 mg Tablet 0.23 USD tablet
        First Prev Next Last
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents
        Country Patent Number Approved Expires (estimated)
        United States 6607748 2000-06-29 2020-06-29
        Properties
        State solid
        Experimental Properties
        Property Value Source
        melting point 87 °C PhysProp
        water solubility Sparigly soluble Not Available
        logP 2.9 Not Available
        Predicted Properties
        Property Value Source
        water solubility 2.90e-01 g/l ALOGPS
        logP 2.68 ALOGPS
        logP 3.13 ChemAxon
        logS -3.1 ALOGPS
        pKa (strongest basic) 7.09 ChemAxon
        physiological charge 1 ChemAxon
        hydrogen acceptor count 4 ChemAxon
        hydrogen donor count 0 ChemAxon
        polar surface area 42.39 ChemAxon
        rotatable bond count 5 ChemAxon
        refractivity 105.88 ChemAxon
        polarizability 40.12 ChemAxon
        References
        Synthesis Reference Not 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
        Resource Link
        KEGG Compound C07156 Link_out
        PubChem Compound 5533 Link_out
        PubChem Substance 46506648 Link_out
        ChemSpider 5332 Link_out
        ChEBI 9654 Link_out
        ChEMBL 9654 Link_out
        Therapeutic Targets Database DAP000104 Link_out
        PharmGKB PA451744 Link_out
        IUPHAR 213 Link_out
        Guide to Pharmacology 213 Link_out
        Drug Product Database 2249804 Link_out
        RxList http://www.rxlist.com/cgi/generic/traz.htm Link_out
        Drugs.com http://www.drugs.com/trazodone.html Link_out
        Wikipedia http://en.wikipedia.org/wiki/Trazodone Link_out
        ATC Codes
        • N06AX05
        AHFS Codes
        • 28:16.04.24
        PDB Entries Not Available
        FDA label show (151 KB)
        MSDS show (73.7 KB)
        Interactions
        Drug Interactions
        Drug Interaction
        Almotriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Aminoglutethimide The 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.
        Amiodarone The 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.
        Amitriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Amoxapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Amprenavir The 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.
        Aprepitant The 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.
        Atazanavir The 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.
        Bosentan The 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.
        Bromocriptine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Buspirone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Cabergoline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Carbamazepine The 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.
        Cimetidine The 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.
        Citalopram Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Clarithromycin The 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.
        Clomipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Clotrimazole The 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.
        Conivaptan The 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.
        Cyclosporine The 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 etexilate P-Glycoprotein inducers such as trazodone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
        Darunavir The 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.
        Delavirdine The 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.
        Desipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Dexamethasone The 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.
        Dextromethorphan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Dihydroergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Diltiazem The 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.
        Donepezil Possible antagonism of action
        Doxepin Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Duloxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Efavirenz The 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.
        Eletriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Ergoloid mesylate Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Ergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Ergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Erythromycin The 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.
        Escitalopram Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Etravirine The 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.
        Fluconazole The 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.
        Fluoxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Fluvoxamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Fosamprenavir The 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.
        Fosphenytoin The 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.
        Frovatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Furazolidone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Galantamine Possible antagonism of action
        Ginkgo biloba Increased effect and toxicity of both agents
        Haloperidol The 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.
        Imatinib The 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.
        Imipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Indinavir The 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.
        Isocarboxazid Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Isoniazid The 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.
        Itraconazole The 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.
        Ketoconazole The 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.
        Lapatinib The 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.
        Lidocaine The 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.
        Linezolid Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Lithium Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Lopinavir The 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.
        Maprotiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Meperidine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Methylergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Metronidazole The 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.
        Miconazole The 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.
        Mirtazapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Moclobemide Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Nafcillin The 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.
        Naratriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Nefazodone 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.
        Nelfinavir The 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.
        Nevirapine The 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.
        Nicardipine The 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.
        Norfloxacin The 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.
        Nortriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Oxcarbazepine The 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.
        Paroxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Pentobarbital The 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.
        Pergolide Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Phenelzine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Phenobarbital The 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.
        Phenytoin The 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.
        Posaconazole The 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.
        Primidone The 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.
        Procarbazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Promethazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Protriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Quinidine The 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.
        Rasagiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Rifabutin The 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.
        Rifampin The 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.
        Rifapentine The 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.
        Ritonavir The 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.
        Rivastigmine Possible antagonism of action
        Rizatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        S-Adenosylmethionine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Saquinavir The 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.
        Selegiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Sertraline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Sibutramine Increased risk of serotonin syndrome. Avoid concomitant therapy.
        Sitaxentan The 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 Wort Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Sumatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Tamoxifen Trazodone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
        Tamsulosin Trazodone, 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.
        Telithromycin The 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.
        Tetracycline The 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.
        Tipranavir The 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.
        Tramadol The use of two serotonin modulators, such as trazodone and tramadol, may increase the risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
        Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Triprolidine The CNS depressants, Triprolidine and Trazodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
        Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Verapamil The 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.
        Voriconazole Voriconazole, 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.
        Zolmitriptan Use 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 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. 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 2C receptor

        Pharmacological action: yes
        Actions: agonist

        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. 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

        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. 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 1A receptor

        Pharmacological action: yes
        Actions: partial agonist

        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. 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

        Pharmacological action: unknown
        Actions: antagonist

        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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

        Organism class: human
        UniProt ID: P35367 Link_out
        Gene: HRH1 Link_out
        Protein Sequence: FASTA
        Gene 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. 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

        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. 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

        Pharmacological action: no
        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
        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

        Actions: substrate

        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. 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

        Actions: substrate

        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.

        3. Cytochrome P450 3A7

        Actions: substrate

        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.

        4. Cytochrome P450 2D6

        Actions: substrate

        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. 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
        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
        Carriers

        1. Alpha-1-acid glycoprotein 1

        Appears to function in modulating the activity of the immune system during the acute-phase reaction

        UniProt ID: P02763 Link_out
        Gene: ORM1 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        SNPs: SNPJam Report Link_out

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