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Which SSRI has the most anticholinergic activity?
Paroxetine (Paxil) is an SSRI that, unlike the other SSRIs, can have anticholinergic effects similar to the tricyclic antidepressants (TCAs). This can result in significant cognitive impairments even at therapeutic doses.
Among currently available selective serotonin reuptake inhibitors (SSRIs), paroxetine exhibits the greatest anticholinergic activity.
In vitro binding studies show paroxetine’s affinity for muscarinic M₁ receptors with a nmol/L, compared to sertraline’s
nmol/L and escitalopram’s
nmol/L.
Clinical and animal studies corroborate these findings, demonstrating anticholinergic effects—such as dry mouth, constipation, and blurred vision—at therapeutic paroxetine plasma levels via blockade of oxotremorine-induced responses.
What other antidepressants are anticholinergic and what problems may patients experience as a result of this effect?
No newer SSRI has surpassed paroxetine in muscarinic antagonism in recent comparative pharmacology reviews.[1][2]
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