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Differences between tricyclic antidepressants and SNRIs mechanism of action

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Answering your questions about these 2 types of antidepressants:

Tricyclic antidepressants (TCAs) are an important group of antidepressants in clinical practice; this drug class includes imipramine, amitriptyline, clomipramine, and desipramine. The main pharmacological effect on presynaptic 5-HT and norepinephrine receptors is the same that SNRIs. This is, they block the reuptake protein that acts as transporter in the nerve terminal. TCAs have very little effect on dopamine reuptake.

TCAs adverse effects are determined by they blockade on cholinergic, adrenergic and histamine transmission

What gives TCAs a different adverse effects profile is their ability to block muscarinic, alpha 1 adrenergic and histamine H1 receptors. The blockade of these receptors gives as a result:


  • Anticholinergic (atropine-like) effects: blurred vision, xerostomia, urinary retention, constipation and narrow angle glaucoma.
  • Sympatholytic effects (alpha 1 blockade): postural hypotension, dizziness and reflex tachicardia.
  • Histamine (H1) antagonism: sedation.



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