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

• ChemBase ID: 538
• Molecular Formular: C19H22ClN5O
• Molecular Mass: 371.86388
• Monoisotopic Mass: 371.15128803
• SMILES: Clc1cc(N2CCN(CC2)CCCn2nc3n(c2=O)cccc3)ccc1
• Canonical SMILES: Clc1cccc(c1)N1CCN(CC1)CCCn1nc2n(c1=O)cccc2
• 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
• InChIKey: PHLBKPHSAVXXEF-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-3-one
• IUPAC Traditional name: trazodone
• Brand Name: Beneficat; Bimaran; Desirel; Desyrel; Molipaxin; Pragmazone; Sideril; Thombran; Tombran; Trazalon; Trazodil; Trazodon; Trazolan; Trazonil; Trialodine; Trittico; Desyrel Dividose
• Synonyms: Trazodonum [INN-Latin]; Trazodona [INN-Spanish]; Trazodone Hcl; Trazodone Hydrochloride; trazodone; Trazodone

Database IDs

• CAS Number: 19794-93-5
• PubChem SID: 160964001; 46506648
• PubChem CID: 5533
• CHEBI ID: 9654
• ATC CODE: N06AX05
• CHEMBL: 621
• Chemspider ID: 5332
• DrugBank ID: DB00656
• IUPHAR ligand ID: 213
• KEGG ID: D08626
• Unique Ingredient Identifier: YBK48BXK30
• Wikipedia Title: Trazodone
• Medline Plus: a681038

CALCULATED PROPERTIES

JChem

• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): 1.5380111
• LogD (pH = 7.4): 2.9594436
• Log P: 3.1318567
• Molar Refractivity: 105.8796 cm^3
• Polarizability: 39.210217 Å^3
• Polar Surface Area: 42.39 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.68
• LOG S: -3.11
• Solubility (Water): 2.90e-01 g/l

PROPERTIES

Physical Property

• Solubility: Sparigly soluble
• Hydrophobicity(logP): 2.9

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: High
• Excretion: 20% feces,; 80% urine
• Half Life: 3-6 hours
• Metabolism: Hepatic
• Legal Status: Pharmacist only (Australia); POM (UK); Rx-only (US)
• Pregnancy Category: C (US)

DETAILS

DrugBank - DB00656

• Drug Groups: approved; investigational
• Description: A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309)
• Indication: For the treatment of depression.
• Pharmacology: 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.
• Toxicity: LD₅₀=96mg/kg (i.v. in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: 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.
• Absorption: Rapidly and almost completely absorbed following oral administration. Food may decrease the rate and extent of absorption.
• Half Life: Undergoes biphasic elimination with an initial phase t_{1/2 α} of 3-6 hours and a terminal phase t_{1/2 β} of 5-9 hours.
• Protein Binding: 89-95% bound to plasma proteins in vitro
• References: 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] ; 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] ; 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] ; 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] ; 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] ; 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] ; 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: Wikipedia; RxList; Drugs.com

REFERENCES

• 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
• 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
• 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
• 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
• 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
• 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
• 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