Similar to fluoxetine, trazodone inhibits the reuptake of serotonin, although trazodone is less potent than fluoxetine in this regard. Antidepressant activity is believed to be produced by blocking the reuptake of serotonin at the presynaptic neuronal membrane. Long-term therapy also can affect postsynaptic neuronal receptor binding sites. There is some evidence in animals that norepinephrine release is enhanced by trazodone. Trazodone does not inhibit monoamine oxidase.
Anticholinergic activity is lower with trazodone than with the tricyclic antidepressants.
Total sleep time is increased, but unlike the tricyclics, trazodone does not affect stage 4 sleep. Trazodone has weak skeletal muscle-relaxant activity and no anticonvulsant activity. Unlike the tricyclics, trazodone has no direct quinidine-like action on the cardiovascular system. Hypotension may be a result of lowered arterial blood pressure caused by the blocking of pressor response to norepinephrine. Trazodone may affect the endocrine system, but results are inconclusive.