Top Gene Interactions
- 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. 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.
- Uses/Sources: For the treatment of depression.
- Treatment: There is no specific antidote for Trazodone. Treatment should be symptomatic and supportive in the case of hypotension or excessive sedation. Any patient suspected of having taken an overdose should have the stomach emptied by gastric lavage. Forced diuresis may be useful in facilitating elimination of the drug. (L1712)
- Route of Exposure: Rapidly and almost completely absorbed following oral administration. Food may decrease the rate and extent of absorption.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 96mg/kg (Intravenous, Mouse) (A308)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Muscarinic acetylcholine receptor M1
Muscarinic acetylcholine receptor M2
Muscarinic acetylcholine receptor M3
Muscarinic acetylcholine receptor M4
5-hydroxytryptamine receptor 2C
5-hydroxytryptamine receptor 2B
Sodium-dependent dopamine transporter
5-hydroxytryptamine receptor 2A
5-hydroxytryptamine receptor 1A
Sodium-dependent serotonin transporter
Alpha-1A adrenergic receptor
Alpha-2A adrenergic receptor
Sodium-dependent noradrenaline transporter
Histamine H1 receptor
Alpha-1B adrenergic receptor
|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.||
Trazodone Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Diabetes Mellitus, Experimental||7.7||
|Alcoholic liver cirrhosis||7.37||
|Carcinoma, Ductal, Breast||7.21||
|Cell Transformation, Neoplastic||7.05||
|Adenomatous Polyposis Coli||6.97||