Comparison of the anticholinergic effects of the serotonergic antidepressants, paroxetine, fluvoxamine and clomipramine

Paroxetine, a selective serotonin reuptake inhibitor, shows relatively high affinity for muscarinic acetylcholine receptors compared to other selective serotonin reuptake inhibitors. To determine whether paroxetine has anticholinergic effects in vivo, we examined the effects of paroxetine on oxotremorine-induced tremor, spontaneous defecation and passive avoidance performance using mice and compared the results with those using fluvoxamine, another selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant with serotonin selectivity. The potency of antidepressant activity as determined in the tail suspension test was paroxetine>fluvoxamine>clomipramine. Paroxetine and clormpramine inhibited oxotremorine-induced tremor, reduced spontaneous defecation and impaired passive avoidance performance, while fluvoxamine did not have similar effects. A comparison of ED50 values showed that the ratio of anticholinergic effect to antidepressant activity was fluvoxamine, >3.2; paroxetine, 2.1-2.6; clomipramine, <0.8. These results suggest that paroxetine may induce fewer adverse anticholinergic effects than clomipramine, but more than fluvoxamine. (C) 2002 Elsevier Science B.V. All rights reserved.