American Board of Psychiatry and Neurology (ABPN) Practice Exam 2026 - Free ABPN Practice Questions and Study Guide

Desipramine is recognized as the least anticholinergic among the listed medications due to its pharmacological profile as a tricyclic antidepressant (TCA). The anticholinergic effects of a drug are primarily associated with its ability to block acetylcholine receptors, which can lead to various side effects such as dry mouth, constipation, urinary retention, and blurred vision.

Desipramine has a higher ratio of norepinephrine reuptake inhibition compared to its anticholinergic activity. This characteristic diminishes its likelihood of causing the typical anticholinergic side effects seen with other TCAs. This profile makes it a better choice for patients who may be sensitive to anticholinergic effects, such as the elderly or those with pre-existing conditions exacerbated by these effects.

In contrast, medications like amitriptyline and nortriptyline have more prominent anticholinergic activity, which correlates with their stronger binding to muscarinic receptors. While imipramine has somewhat less anticholinergic action than amitriptyline, it still does not surpass desipramine in this regard. Consequently, desipramine stands out as the preferable option when minimizing anticholinergic side effects