What is the pharmacology of trazodone?

Answer: Trazodone is a medicine that is used for treating depression and anxiety. Trazodone primarily acts as an antagonist of serotonin 2A and alpha 1 noradrenergic receptors.

trazodone pharmacology

Trazodone is a medication that is used for the clinical treatment of major depressive disorder, anxiety, alcohol addiction, insomnia, obsessive compulsive disorder (OCD), and schizophrenia. It is orally administered, and predominantly metabolized by the liver enzyme CYP3A4.

Pharmacologically, trazodone has several targets of action that can account for its ability to change a person's behaviour. For one, it acts as an antagonist that blocks serotonin 2A receptors (5-HT2A) in the brain. This receptor is usually an inhibitory G-protein coupled receptor. The receptor itself seems to be upregulated in patients with depression (Regulation of central 5-HT2A receptors: a review of in vivo studies).

Trazodone acts as a serotonin reuptake inhibitor as well. By blocking reuptake, it enhances the amount of serotonin at synapses. Inhibition of the serotonin reuptake machinery by the action of trazodone or other classical antidepressant drugs such as SSRIs decreases the expression of the 5-HT2A receptor. This decrease in receptor expression is likely a pharmacodynamic change by the neurons in an attempt to maintain homeostasis.

Because it has both actions at the serotonin signaling system, it can also be called a SARI, or serotonin antagonist and reuptake inhibitor.

Trazodone is a dirty drug, meaning it has sites of action at many different protein targets. One other site where it acts as an antagonist is at the alpha 1 adrenergic receptors. This receptor is a Gq coupled metabotropic receptor. By blocking this receptor, trazodone may contribute to orthostatic hypotension, the condition where a person's blood pressure drops rapidly when moving to a vertical position.

Some other biologically relevant targets of trazodone include the histamine H1 receptor, 5-HT2B receptor, 5-HT2C receptors and the 5-HT7 receptor.

During metabolism, trazodone is converted into meta-chlorophenylpiperazine, or mCPP. This substance is also active and has action at many different molecular targets.