Evaluation of Brain Anticholinergic Activities of Urinary Spasmolytic Drugs Using a High-Throughput Radio Receptor Bioassay

Abstract

Tolterodine and fesoterodine appear to have the highest pharmacodynamic potential to induce central anticholinergic side effects of the tested USDs. Darifenacin displayed the lowest AA, and combined with a low degree of brain distribution, it has probably the most favorable pharmacological profile of the USDs with respect to risk of cognitive impairment in older adults.

Flexible‐Dose Fesoterodine in Elderly Adults with Overactive Bladder: Results of the Randomized, Double‐Blind, Placebo‐Controlled Study of Fesoterodine in an Aging Population Trial

“…A recent study showed no adverse effect of fesoterodine on memory or executive function in a group of cognitively intact older adults, 36 despite the high anticholinergic activity of the metabolite of fesoterodine: 5-hydroxymethyl tolterodine. 37 Unlike typical studies of antimuscarinics for OAB, this study included a large proportion of men (47%), which is consistent with epidemiological data on the prevalence of OAB. 5 Of the men in this trial, 41% had benign prostatic enlargement recorded as a coexisting medical condition.…”

Comedication and Treatment Length in Users of Acetylcholinesterase Inhibitors

“…In our study, only 11% of the urologic spasmolytic users were prescribed darifenacin. However, due to drug interactions with inhibitors of P-glycoprotein and individual variability in brain permeability, urologic spasmolytics as well as other drugs with any central anticholinergic effect, regardless of the dose, are not recommended to people with dementia [28]. …”

“…The basis for the ADS score evaluation is a list of drugs and their anticholinergic scores [27] founded on previously published classifications and studies [16, 18, 19, 28]. The ADS score is from 0 to 3, where 0 is defined as “no anticholinergic activity,” 1 as “potentially anticholinergic,” 2 as “clinically significantly anticholinergic,” and 3 as “strong anticholinergic activity.” The ADS score for each AChEI user was calculated as the sum of the ADS scores for each different drug prescribed during the 6-month coprescription window.…”

Cognitive impact of anticholinergic medication in MS: Adding insult to injury?

“…However, reports of memory problems, hallucinations and confusion (Tsao and Heilman, 2003;Womack and Heilman, 2003;Williams and Staudenmeier, 2004;Salvatore et al, 2007) raise concerns regarding the potential cognitive impact of tolterodine. Also, a recent in vitro study suggested that tolterodine has a very high pharmacodynamic potential to generate central anticholinergic side effects, compared to other ACD used for bladder symptoms (Jakobsen et al, 2011).…”