Which neurotransmitter is primarily targeted by tricyclic antidepressants (TCAs)?

Tricyclic antidepressants (TCAs) primarily target norepinephrine, which is a key neurotransmitter in the regulation of mood and emotional responses. These medications work by inhibiting the reuptake of norepinephrine and serotonin in the synaptic cleft, thereby increasing the levels of these neurotransmitters available to bind to their respective receptors in the brain.

While TCAs also have effects on serotonin, their stronger and more pronounced action on norepinephrine is a defining characteristic of their pharmacological profile. By elevating norepinephrine levels, TCAs can help alleviate symptoms of depression and improve mood, making them effective in treating depressive disorders.

Moreover, the other neurotransmitters listed—dopamine and GABA—are not the primary targets of TCAs. While some antidepressants may interact with these systems, they play a lesser role in the mechanism of action of tricyclics compared to norepinephrine.