Please Wait
Applying Filters...
Menu
Xls
2D Structure
Also known as: 19794-93-5, Trazodon, Trittico, Trazodona, Trazodonum, Trazodonum [inn-latin]
Molecular Formula
C19H22ClN5O
Molecular Weight
371.9  g/mol
InChI Key
PHLBKPHSAVXXEF-UHFFFAOYSA-N
FDA UNII
YBK48BXK30

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)
Trazodone is a Serotonin Reuptake Inhibitor.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one
2.1.2 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
2.1.3 InChI Key
PHLBKPHSAVXXEF-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1CN(CCN1CCCN2C(=O)N3C=CC=CC3=N2)C4=CC(=CC=C4)Cl
2.2 Other Identifiers
2.2.1 UNII
YBK48BXK30
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Af 1161

2. Af-1161

3. Af1161

4. Apo Trazodone

5. Apo-trazodone

6. Deprax

7. Desyrel

8. Gen Trazodone

9. Gen-trazodone

10. Molipaxin

11. Novo Trazodone

12. Novo-trazodone

13. Nu Trazodone

14. Nu-trazodone

15. Pms Trazodone

16. Pms-trazodone

17. Ratio Trazodone

18. Ratio-trazodone

19. Ratiotrazodone

20. Thombran

21. Tradozone

22. Trazodon Hexal

23. Trazodon Neuraxpharm

24. Trazodon-neuraxpharm

25. Trazodone Hydrochloride

26. Trazodonneuraxpharm

27. Trazon

28. Trittico

2.3.2 Depositor-Supplied Synonyms

1. 19794-93-5

2. Trazodon

3. Trittico

4. Trazodona

5. Trazodonum

6. Trazodonum [inn-latin]

7. Trazodona [inn-spanish]

8. Trialodine

9. Trazodone (inn)

10. Trazodone Free Base

11. Beneficat

12. Desirel

13. Sideril

14. Trazalon

15. Trazodil

16. Trazonil

17. Chembl621

18. Ybk48bxk30

19. 1,2,4-triazolo(4,3-a)pyridin-3(2h)-one, 2-(3-(4-(3-chlorophenyl)-1-piperazinyl)propyl)-

20. 1,2,4-triazolo[4,3-a]pyridin-3(2h)-one, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-

21. Chebi:9654

22. Oleptro

23. 19794-93-5 (free)

24. 2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}[1,2,4]triazolo[4,3-a]pyridin-3(2h)-one

25. Trazodonum [latin]

26. Trazodona [spanish]

27. J10.767k

28. Trazodone [inn]

29. Trazodone [inn:ban]

30. 2-(3-[4-(3-chlorophenyl)-1-piperazinyl]propyl)[1,2,4]triazolo[4,3-a]pyridin-3(2h)-one

31. S-triazolo(4,3-a)pyridin-3(2h)-one, 2-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-

32. 1,2,4-triazolo(4,3-a)pyridin-3(2h)-one, 2-(3-(4-(3-chlorophenyl)-1-piperazinyl)propyl)-,

33. Trittico (tn)

34. 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4,5-a]pyridin-3-one

35. Ncgc00016035-02

36. Einecs 243-317-1

37. Cas-25332-39-2

38. Unii-ybk48bxk30

39. Brn 0628010

40. 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one

41. Spectrum_001424

42. Trazodone [mi]

43. Prestwick0_000292

44. Prestwick1_000292

45. Prestwick2_000292

46. Prestwick3_000292

47. Spectrum2_000854

48. Spectrum3_001560

49. Spectrum4_000755

50. Spectrum5_000974

51. Lopac-t-6154

52. Trazodone [vandf]

53. Ec 243-317-1

54. Trazodone [who-dd]

55. Lopac0_001159

56. Oprea1_185901

57. Schembl28167

58. Bspbio_000224

59. Bspbio_003040

60. Gtpl213

61. Kbiogr_001110

62. Kbioss_001904

63. Divk1c_000196

64. Spbio_000867

65. Spbio_002443

66. Bpbio1_000248

67. Dtxsid5045043

68. Hsdb 7048

69. Kbio1_000196

70. Kbio2_001904

71. Kbio2_004472

72. Kbio2_007040

73. Kbio3_002540

74. Ninds_000196

75. Zinc538483

76. Amy32533

77. Bcp07176

78. Bdbm50073444

79. S5857

80. Akos015896423

81. Ac-6778

82. Ccg-205233

83. Db00656

84. Sdccgsbi-0051126.p004

85. 2-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2h)-one

86. Idi1_000196

87. Ncgc00016035-01

88. Ncgc00016035-03

89. Ncgc00016035-04

90. Ncgc00016035-05

91. Ncgc00016035-06

92. Ncgc00016035-07

93. Ncgc00016035-08

94. Ncgc00016035-09

95. Ncgc00016035-10

96. Ncgc00016035-12

97. Ncgc00016035-25

98. Ncgc00024405-03

99. 8-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-1,7,8-triazabicyclo[4.3.0]nona-2,4,6-trien-9-one Hydrochloride

100. Sbi-0051126.p003

101. Ft-0658382

102. C07156

103. D08626

104. Ab00053648-14

105. Ab00053648_15

106. Ab00053648_16

107. 794t935

108. L000771

109. Q411457

110. Brd-k70778732-003-05-1

111. Brd-k70778732-003-15-0

112. 2-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-s-triazolo(4,3-a)pyridin-3(2h)-one

113. 2-(3-[4-(3-chlorophenyl)-1-piperazinyl]propyl)[1,2,4]triazolo[4,3-a]pyridin-3(2h)-one #

114. 2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-2h,3h-[1,2,4]triazolo[4,3-a]pyridin-3-one

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 371.9 g/mol
Molecular Formula C19H22ClN5O
XLogP32.8
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count4
Rotatable Bond Count5
Exact Mass371.1512880 g/mol
Monoisotopic Mass371.1512880 g/mol
Topological Polar Surface Area42.4 Ų
Heavy Atom Count26
Formal Charge0
Complexity611
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Serotonin Uptake Inhibitors

National Library of Medicine's Medical Subject Headings. Trazodone. Online file (MeSH, 2016). Available from, as of January 19, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html


/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Trazodone is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of March 17, 2016: https://clinicaltrials.gov/ct2/results?term=trazodone&Search=Search


Trazodone hydrochloride tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of trazodone hydrochloride tablets has been established in trials with the immediate release formulation of trazodone. /Included in US product label/

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of February 29, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


Although trazodone has been used in the treatment of schizophrenic disorder, the drug is less effective than chlorpromazine. Depressive symptomatology may improve during trazodone therapy, but the drug does not appear to relieve psychotic symptoms in most schizophrenic patients. Based on limited data, trazodone has little value when used alone in patients with chronic schizophrenic disorder without depression; however, it may be a useful adjunct to antipsychotic agents (e.g., phenothiazines) in patients with chronic schizophrenic disorder and associated depression. Unlike tricyclic antidepressants, trazodone does not appear to worsen psychotic symptoms in these patients. /NOT included in US product label/

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2378


For more Therapeutic Uses (Complete) data for TRAZODONE (11 total), please visit the HSDB record page.


4.2 Drug Warning

/BOXED WARNING/ WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of trazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone hydrochloride tablets are not approved for use in pediatric patients.

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of February 29, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of February 29, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


The development of a potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with antidepressants alone and may occur with trazodone treatment, but particularly with concomitant use of other serotoninergic drugs (including SSRIs, SNRIs and triptans) and with drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors (MAOIs)), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes.

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of February 29, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described for clinical worsening and suicide risk represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that trazodone hydrochloride tablets is not approved for use in treating bipolar depression.

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of February 29, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


For more Drug Warnings (Complete) data for TRAZODONE (32 total), please visit the HSDB record page.


4.3 Drug Indication

Trazodone is indicated for the treatment of major depressive disorder (MDD). It has been used off-label for adjunct therapy in alcohol dependence, and off-label to treat anxiety and insomnia. It may also be used off-label to treat symptoms of dementia, Alzheimers disease, schizophrenia, eating disorders, and fibromyalgia due to its effects on various neurotransmitter receptors.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Trazodone treats depressed mood and other depression-related symptoms and shows benefit in the treatment of insomnia due to its sedating effects. It is known to prolong the cardiac QT-interval. Memory, alertness, and cognition may be decreased by trazodone, especially in elderly patients due to its central nervous system depressant effects. A note on priapism Trazodone has been associated with the occurrence of priapism, a painful and persistent incidence of penile tissue erection that is unrelievable and can cause permanent neurological damage if left untreated. Patients must be advised to seek immediate medical attention if priapism is suspected.


5.2 MeSH Pharmacological Classification

Anti-Anxiety Agents

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. (See all compounds classified as Anti-Anxiety Agents.)


Selective Serotonin Reuptake Inhibitors

Compounds that specifically inhibit the reuptake of serotonin in the brain. (See all compounds classified as Selective Serotonin Reuptake Inhibitors.)


Antidepressive Agents, Second-Generation

A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake. (See all compounds classified as Antidepressive Agents, Second-Generation.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
TRAZODONE
5.3.2 FDA UNII
YBK48BXK30
5.3.3 Pharmacological Classes
Serotonin Reuptake Inhibitor [EPC]
5.4 ATC Code

N06AX05

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


N - Nervous system

N06 - Psychoanaleptics

N06A - Antidepressants

N06AX - Other antidepressants

N06AX05 - Trazodone


5.5 Absorption, Distribution and Excretion

Absorption

Trazodone is rapidly absorbed in the gastrointestinal tract after oral administration, with a bioavailability ranging from 63-91% and an AUC0t of 18193.0 ngh/mL. Food may impact absorption in a variable fashion, and may sometimes lead to decreases in the Cmax of trazodone. In the fed state in 8 healthy volunteers, the Cmax was measured to be 1.47 +/- 0.16 micrograms/mL, and in the fasted state, was measured at 1.88 +/- 0.42 micrograms/mL. The average Tmax after a single dose of 300 mg was 8 hours. Food may increase absorption by up to 20%.


Route of Elimination

Less than 1% of an oral dose is excreted unchanged in the urine. In a pharmacokinetic study, about 60-70% of radiolabeled was excreted urine within 48 hours. Approximately 9-29% was found to be excreted in feces over a range of 60 to 100 hours. According to the FDA medical review, the kidneys are responsible for 70 to 75% of trazodone excretion. About 21% of trazodone is reported to be excreted by the fecal route and 0.13% of the parent drug is eliminated in the urine as unchanged drug.


Volume of Distribution

A single-dose pharmacokinetic study of 8 volunteers taking trazodone determined a volume of distribution of 0.84 +/- 0.16 L/kg. The FDA medical review of trazodone reports a volume of distribution of 0.47 to 0.84 L/kg.


Clearance

A decrease in total apparent clearance (5.1 versus 10.8 L/h) was seen elderly volunteers in the fasted state when compared with younger volunteers. Another pharmacokinetic study determined the total body clearance of trazodone to be 5.3 +/- 0.9 L/hr in 8 healthy patients taking a single dose of trazodone.


Following oral administration of single doses of 25, 50, or 100 mg of trazodone to healthy, fasted adults in another study, mean peak plasma trazodone concentrations were 490, 860, and 1620 ng/mL, respectively. The areas under the plasma concentration-time curves (AUCs) were 3.44, 5.95, and 11.19 ug-hr/mL, for the 25-, 50-, and 100-mg doses, respectively. Limited crossover data are available comparing AUCs in fasted and nonfasted patients; however, it appears that the presence of food slightly increases the AUC for trazodone.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2381


Following oral administration of a single 25-mg dose of radiolabeled trazodone to healthy adults in one study, mean peak plasma drug concentrations of 650 and 480 ng/mL occurred at 1.5 and 2.5 hours after ingestion, in the fasted and nonfasted state, respectively.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2381


/MILK/ The excretion of breast milk was studied in six lactating women following the oral administration of a single trazodone tablet (50 mg). The milk/plasma ratio of trazodone based on area under the plasma and milk curves was small: 0.142 +/- 0.045 (mean +/- s.d.). Assuming that the babies would drink 500 mL 12 h-1, they would be exposed to less than 0.005 mg kg-1 as compared to 0.77 mg kg-1 for the mothers. It is concluded that exposure of babies to trazodone via breast milk is very small.

PMID:3768252 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401139 Verbeeck RK et al; Br J Clin Pharmacol. 1986 Sep;22(3):367-70 (1986)


Peak plasma concentrations of trazodone occur approximately 1 hour after oral administration when the drug is taken on an empty stomach or 2 hours after oral administration when taken with food. Following oral administration of multiple doses of trazodone (25 mg 2 or 3 times daily), steady-state plasma concentrations of the drug are usually attained within 4 days and exhibit wide interpatient variation.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2381


For more Absorption, Distribution and Excretion (Complete) data for TRAZODONE (8 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Trazodone is heavily metabolized and activated in the liver by CYP3A4 enzyme to the active metabolite, m-chlorophenylpiperazine (mCPP). The full metabolism of trazodone has not been well characterized. Some other metabolites that have been identified are a dihydrodiol metabolite and carboxylic acid.


Trazodone is extensively metabolized in the liver via hydroxylation, oxidation, N-oxidation, and splitting of the pyridine ring. A hydroxylated metabolite and oxotriazolopyridinpropionic acid (an inactive metabolite excreted in urine) are conjugated with glucuronic acid. Results of in vitro studies indicate that metabolism of trazodone to an active metabolite, m-chlorophenylpiperazine, is mediated by the cytochrome P-450 (CYP) 3A4 isoenzyme. The manufacturers state that other metabolic pathways involved in metabolism of trazodone have not been well characterized. Results from animal studies indicate that trazodone does not induce its own metabolism.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2382


In vitro studies in human liver microsomes show that trazodone is metabolized, via oxidative cleavage, to an active metabolite, m-chlorophenylpiperazine (mCPP) by CYP3A4. Other metabolic pathways that may be involved in the metabolism of trazodone have not been well characterized. Trazodone is extensively metabolized; less than 1% of an oral dose is excreted unchanged in the urine.

NIH; DailyMed. Current Medication Information for Trazodone Hydrochloride (Trazodone Hydrochloride) Tablet, Film Coated (Updated: August 2015). Available from, as of January 26, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=324d2543-477d-4c0b-bfa0-d76cb4e5cd48


Approximately 70-75% of an oral dose of trazodone is excreted in urine within 72 hours of administration, principally as metabolites. About 20% of an oral dose of trazodone is excreted in urine as oxotriazolopyridinpropionic acid and its conjugates, and about 10% as a dihydrodiol metabolite; less than 1% of a dose is excreted unchanged. The remainder of an oral dose of the drug is excreted in feces via biliary elimination, principally as metabolites.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2382


Trazodone has known human metabolites that include 1-(3-Chlorophenyl)piperazine, Trazodone epoxide, and p-Hydroxytrazodone.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560


5.7 Biological Half-Life

The plasma elimination half-life was markedly prolonged (13.6 versus 6 hours) elderly volunteers in the fasted state when compared with younger volunteers. Another study of 8 healthy individuals taking a single dose of trazodone indicated a terminal elimination half-life of 7.3 +/- 0.8 hr. A two-phase pattern of trazodone elimination has been reported. Initially, the half-life is reported to range from 3 to 6 hours and the second phase of elimination to range from 5 to 9 hours.


The half-life of trazodone in the initial phase is about 3-6 hours and the half-life in the terminal phase is about 5-9 hours.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2382


... Following IV administration /of trazodone HCl to beagle dogs/, the mean +/- SD elimination half-life /was/ 169 +/- 53 minutes ... . Following oral administration, the mean +/- SD elimination half-life /was/ 166 +/- 47 minutes ... .

PMID:24168312 Jay AR et al; Am J Vet Res 74 (11): 1450-6 (2013)


In dogs after 8 mg/kg IV, volume of distribution was (all value are means ) 2.53 L/kg, elimination half life 169 minutes, and plasma total body clearance was 11.15 mL/min/kg. After 8 mg/kg PO, bioavailability was 85%, and elimination half life was 166 minutes, peak plasma levels occurred at 445 minutes (mean), but there was wider inter-subject variation (+ or - 271 minutes).

Plumb D.C. Veterinary Drug Handbook. 8th ed. (pocket). Ames, IA: Wiley-Blackwell, 2015., p. 1438


5.8 Mechanism of Action

The mechanism of action of trazodone is not fully understood, however, it is known to inhibit the reuptake of serotonin and block both histamine and alpha-1-adrenergic receptors. Despite the fact that trazodone is frequently considered a selective serotonin reuptake inhibitor, several reports have shown that other mechanisms including antagonism at serotonin 5-HT1a, 5-HT1c, and 5-HT2 receptor subtypes may occur. The strongest antagonism of trazodone is reported to occur at the serotonin 5-HT21c receptors, preventing serotonin uptake. In addition to acting on serotonin receptors, trazodone has been shown to inhibit serotonin transporters. The antidepressant effects of trazodone result from the inhibition of receptor uptake, which normally decreases circulating neurotransmitters, contributing to depressive symptoms.


The precise mechanism of antidepressant action of trazodone is unclear, but the drug has been shown to selectively block the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane. The effects of serotonin may thus be potentiated. Unlike other antidepressant agents (e.g., tricyclic antidepressants), trazodone may have a dual effect on the central serotonergic system. Animal studies indicate that trazodone acts as a serotonin agonist at high doses (6-8 mg/kg), while at low doses (0.05-1 mg/kg), it antagonizes the actions of serotonin. Trazodone does not appear to influence the reuptake of dopamine or norepinephrine within the CNS; however, animal studies indicate that trazodone may enhance release of norepinephrine from neuronal tissue. Trazodone does not cause serotonin release in vitro.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2380