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Updated: May 31, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Published on: February 11, 2019

Effect of oxybutynin and imidafenacin on central muscarinic receptor occupancy and cognitive function: a monkey PET

Shigeyuki Yamamoto1, Shuji Maruyama, Yoshihiko Ito

  • 1Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden.

Neuroimage
|June 30, 2011
PubMed

Insights

Antimuscarinic drugs for overactive bladder can cause cognitive impairment by blocking central muscarinic acetylcholine receptors (mAChR). Imidafenacin showed less cognitive impact than oxybutynin, suggesting lower central mAChR occupancy is key for safer OAB treatments.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Radiochemistry

Background:

  • Antimuscarinic agents are common treatments for overactive bladder (OAB).
  • These drugs can cause side effects like dry mouth and cognitive impairment.
  • Central muscarinic acetylcholine receptor (mAChR) occupancy is implicated in these side effects.

Purpose of the Study:

  • To investigate the effects of oxybutynin and imidafenacin on cognitive function and central mAChR occupancy in conscious monkeys.
  • To determine the relationship between mAChR occupancy and cognitive impairment.
  • To identify potential thresholds for central mAChR occupancy to avoid cognitive side effects.

Main Methods:

  • Positron emission tomography (PET) scans were performed on three conscious monkeys (Macaca mulatta).
  • A mAChR radioligand, N-[(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB), was used.
  • Scans were conducted before and at 1, 4, and 24 hours after oral administration of oxybutynin or imidafenacin.

Main Results:

  • Oxybutynin induced dose-dependent cognitive impairment, peaking at 1 hour post-administration.
  • Significant positive correlations were found between mAChR occupancy and cognitive impairment in various brain regions, particularly the brainstem and cortices.
  • Imidafenacin did not cause significant cognitive impairment, despite some central mAChR occupancy.

Conclusions:

  • Central mAChR occupancy thresholds for cognitive impairment are approximately 30-40% in cortices and 20-30% in the brainstem.
  • Drugs for OAB treatment should ideally maintain central mAChR occupancy below these thresholds to minimize cognitive side effects.
  • This study provides insights into the neuropharmacology of antimuscarinic agents and OAB treatment.

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