What is the main mechanism of action for most tricyclic antidepressants?

The primary mechanism of action for most tricyclic antidepressants (TCAs) involves the inhibition of the reuptake of both serotonin and norepinephrine. This dual reuptake inhibition increases the levels of these neurotransmitters in the synaptic cleft, which can help alleviate symptoms of depression. By blocking the transporters responsible for the reuptake of serotonin (5-HT) and norepinephrine (NE), TCAs enhance the effects of these neurotransmitters in the brain, which is thought to contribute to their antidepressant effects.

This mechanism contrasts with the more selective antidepressants that primarily target only one of these neurotransmitters. For instance, some agents may primarily inhibit only serotonin reuptake, while others may focus on norepinephrine. Additionally, activating dopamine receptors is not a mechanism associated with TCAs; instead, their therapeutic effects derive mainly from the modulation of serotonin and norepinephrine levels. Understanding this mechanism is important for comprehending how these medications are used to treat various mood disorders.