ChemicalBook > Product Catalog > API > Nervous system drugs > Antidepressants, Antimanics drugs > Trazodone
Trazodone Chemical Properties
- Melting point:86-870C
- Boiling point:528.5±60.0 °C(Predicted)
- Density 1.3141 (rough estimate)
- refractive index 1.5790 (estimate)
- pkapKa (50% ethanol): 6.14(at 25℃)
- CAS DataBase Reference19794-93-5(CAS DataBase Reference)
- NIST Chemistry ReferenceDesyrel(trazodone hcl salt)(19794-93-5)
- EPA Substance Registry System1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]- (19794-93-5)
- RIDADR 3249
- HazardClass 6.1(b)
- PackingGroup III
- Hazardous Substances Data19794-93-5(Hazardous Substances Data)
Trazodone Usage And Synthesis
- Chemical PropertiesBrown Oil
- UsesIt is believed that trazodone, in therapeutic doses, inhibits the neuronal reuptake of serotonin. It is not a MAO inhibitor or a CNS stimulator. It has a minor influence on the reuptake of norepinephrine and dopamine. In addition, it does not bind with cholinergic or α-adrenergic receptors.
- DefinitionChEBI: An N-arylpiperazine in which one nitrogen is substituted by a 3-chlorophenyl group, while the other is substituted by a 3-(3-oxo[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)propyl group.
- IndicationsTrazodone (Apothecon) is also classified as an antidepressant
agent. It is a selective serotonin reuptake inhibitor
(SSRI), partial agonist at postsynaptic 5-HT1A
receptors, and exhibits α-adrenoceptor blocking actions.
Trazodone may cause priapism and enhance libido, and it prolongs nocturnal erections. This drug has been used both orally and by intracavernosal injection. It can be used alone or in combination with yohimbine. Overall, trazodone has not been as effective in treating ED as other available agents. However, it may be an option for selected patients, particularly those with performance anxiety or low libido.
- Manufacturing ProcessIn an initial step, 2-chloropyridine is reacted with semicarbazide to give s_x0002_triazolo-[4,3-a]-pyridine-3-one.
To a boiling solution of 6.7 grams s-triazolo-[4,3-a]-pyridine-3-one in 80 ml
dioxane, there is added 2.4 grams 50% NaH. The mixture is refluxed during 1
hour under stirring, then 13.5 grams 1-(3-chloropropyl)-4-mchlorophenylpiperazine is added. The mixture is refluxed under stirring for 20
hours, cooled, diluted with an equal volume of ether, the sodium chloride
filtered out, and ethereal HCl added. The solid which precipitates is filtered out and crystallized from 95% alcohol. Yield is 13.5 grams, MP 223°C.
The following is an alternative method of preparation: 1 gram 2-(γ-
chloropropyl)-s-triazolo-[4,3-a]-pyridine-3-one and 5 ml saturated ammonia
alcoholic solution are heated for 5 hours in a closed tube at 100°C. The
contents of the tube are cooled, the ammonium chloride filtered out and the
solvent is removed. There remains a residue of 0.9 grams 2-(γ-aminopropyl)-
This residue is dissolved in isopropyl alcohol and 1 gram N-bis-chloroethylaniline is added to it. The mixture is refluxed for 3 hours. The solvent is removed at a reduced pressure, the residue is treated with 50% potassium carbonate, and extracted with ether. By treating with ethereal hydrochloric acid, 2-N'-m-chlorophenylpiperazino-propyl-s-triazole[4,3-a]pyridine-3-one hydrochloride is precipitated; MP 223°C.
- brand nameBeneficat;Bimaran;Deprax;Devidone;Manegan;Molipaxin;Pragmarel;Pragmazone;Taxagon;Thittico;Thombran;Thromban;Tombran;Tramensan;Tritico;Trittico.
- Therapeutic FunctionTranquilizer
- World Health Organization (WHO)Trazodone, an antidepressant indicated for the treatment of a wide range of depressive illness, was introduced in 1973. Although it is registered for use in many countries with highly evolved regulatory authorities, approval for registration was not granted in Norway because of a suspicion of carcinogenicity in a two-year rat study.
- Biological FunctionsTrazodone (Desyrel) was introduced in the early 1980s as a second-generation antidepressant. It blocks the neuronal reuptake of serotonin and is an antagonist at the 5HT2-receptor. Also, its major metabolite, mchlorophenylpiperazine (mCPP), is a postsynaptic serotonin receptor agonist. When compared to the TCAs, trazodone is relatively free of antimuscarinic side effects, but it does block the α-adrenoceptor. Common side effects include marked sedation, dizziness, orthostatic hypotension, and nausea. Priapism is an uncommon but serious side effect requiring surgical intervention in one-third of the cases reported. Because of trazodone’s sedating quality, it is often used in low doses to counter the insomnia associated with the newer antidepressants, such as the SSRIs.
- Mechanism of actionTrazodone acts as an antagonist at 5-HT2A receptors and is a weak inhibitor of 5-HT reuptake at the
presynaptic neuronal membrane, potentiating the synaptic effects of 5-HT. Its mechanism of action is
complicated by the presence of its metabolite, m-chlorophenylpiperazine, which is a 5-HT2C
agonist. At therapeutic dosages, trazodone does not appear to influence the reuptake of dopamine or NE
within the CNS. It has little anticholinergic activity and is relatively devoid of toxic cardiovascular effects. The
increase in serotonergic activity with long-term administration of trazodone decreases the number of
postsynaptic serotonergic (i.e., 5-HT2) and β-adrenergic binding sites in the brains of animals, decreasing the
sensitivity of adenylate (or adenylyl) cyclase to stimulation by β-adrenergic agonists. It has been suggested
that postsynaptic serotonergic receptor modification is mainly responsible for the antidepressant action
observed during long-term administration of trazodone. Trazodone does not inhibit MAO and, unlike
amphetamine-like drugs, does not stimulate the CNS.
Trazodone is rapidly and almost completely absorbed from the GItract following oral administration, with an oral bioavailability of approximately 65%. Peak plasma concentrations of trazodone occur approximately 1 hour after oral administration when taken on an empty stomach or 2 hours when taken with food. At steady state, its plasma concentrations exhibit wide interpatient variation.
Trazodone is extensively metabolized in the liver by N-dealkylation to its primary active metabolite, m-chlorophenylpiperazine (m-CPP), which subsequently undergoes aromatic hydroxylation to p-hydroxy-m-CPP. In vitro studies indicate that CYP3A4 is the major isoform involved in the production of m-CPP from trazodone (and CYP2D6 to a lesser extent). The p-hydroxy-m-CPP and oxotriazolopyridine-propionic acid (the major metabolite excreted in urine) are conjugated with glucuronic acid. Less than 1% of a dose is excreted unmetabolized.
- Clinical UseTrazodone is a phenylpiperazine–triazolopyridine antidepressant that is structurally unrelated to most of the other antidepressant classes.Trazodone is used primarily in the treatment of insomnia, mental depression, or depression/anxiety disorders. The drug also has shown some efficacy in the treatment of benzodiazepine or alcohol dependence, diabetic neuropathy, and panic disorders.
- Chemical SynthesisTrazodone, 2-[3-[4-(m-chlorophenyl)-1-piperazineyl]propyl]-s-triazolo[4,3-a]
piridine-3(2H)-one (7.3.8), is synthesized from 2-chloropiridine, the reaction of which
with semicarbazide gives s-triazolo-3-one[4,3-a]pyridine (7.3.7). Alkylation of this product using 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine gives trazodone (7.3.8)
- Drug interactionsTrazodone possesses serotonergic activity; therefore, the possibility of developing 5-HT syndrome should be considered in patients who are receiving trazodone and other SSRIs or serotonergic drugs concurrently. When trazodone is used concurrently with drugs metabolized by CYP3A4, caution should be used to avoid excessive sedation. Trazodone can cause hypotension, including orthostatic hypotension and syncope; concomitant administration of antihypertensive therapy may require a reduction in dosage of the antihypertensive agent.
- 1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-7,8-dihydro-7,8-dihydroxy- 1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one, 2-(trimethylsilyl)- 2-[3-[Bis(2-chloroethyl)aMino]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one 4’-Hydroxy Trazodone Trazodone-D6 Hydrochloride DOXEPIN Citalopram NA Gabapentin 1-(3-Chlorophenyl)piperazine dihydrochloride TRAZODONE HYDROCHLORIDE USP29/EP5,TRAZODONE HYDROCHIORIDE,TRAZODONE HYDROCHLORIDE,TRAZODONE HCL Isotrazodone Piperazine, 1-(3-broMopropyl)-4-(3-chlorophenyl)- Trazodone Hydrochloride BP Impurity H DiHCl 1-(3-Bromopropyl)-4-(4-chlorophenyl)piperazine Trazodone Impurity 28 4-chloropyridine BIUREA
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