Tricyclic Antidepressants (TCAs)
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Overview
Tricyclic antidepressants are one of the earliest classes of antidepressants, named for their three-ring chemical structure. They inhibit reuptake of serotonin and norepinephrine but also affect histamine, acetylcholine, and alpha-adrenergic receptors, leading to a broader side effect profile than newer antidepressants. Despite this, they remain important for treatment-resistant depression and chronic pain.
How do tricyclic antidepressants (tcas) work?
Tricyclic antidepressants inhibit the reuptake of serotonin and norepinephrine by blocking their respective transporters (SERT and NET), increasing the concentration of these neurotransmitters in the synaptic cleft. However, they are non-selective and also block muscarinic acetylcholine receptors (causing dry mouth, constipation, urinary retention), histamine H1 receptors (causing sedation and weight gain), and alpha-1 adrenergic receptors (causing orthostatic hypotension). Their narrow therapeutic index makes overdose potentially lethal due to cardiac conduction abnormalities.
Drugs in this class
- Amitriptyline (Elavil)