Antidepressants: Mechanisms of Action

pediagenosis    June 10, 2021    Medicine , Pharmacology    Comment   

Antidepressants: Mechanisms of Action

Most antidepressants primarily enhance the action of endogenous amine neurotransmitters; they act indirectly, not binding to 5­HT or NE receptors but enhancing neurotransmitter action by inhibiting metabolism or removing neurotransmitters from synapses. Increased synaptic 5­HT or NE levels then counteract the abnormally low levels that produce depression. 5­HT enhancement may be more important than enhancement of NE, so SSRIs have become popular. MAOIs inhibit metabolism of 5­HT and NE, thus increasing amine levels. Mechanisms of newer drugs include direct binding to 5­HT or NE receptor subtypes (eg, antagonist action at presynaptic α₂­adrenoceptors stimulates NE release). The action of bupropion does not seem to involve 5­HT or NE and therefore may represent a novel mechanism. The long­term mechanism of antidepressant action is unknown. All these drugs modify neurochemical pathways and can elicit adverse effects (eg, sedation and excitation).