Defense Date


Document Type


Degree Name

Master of Science



First Advisor

Dr. Jurgen Venitz


Purpose: To establish a tool, termed as antimuscarinic activity (AMA), to predict the incidence of antimuscarinic adverse events (AMAEs).Methods: A literature review, focused on drugs having off-target interaction with muscarinic receptors, was performed. Prototypical drugs olanzapine, diphenhydramine, paroxetine were selected for the analysis. Scopolamine and darifenacin were included as positive and negative controls, respectively. Physiochemical properties, pharmacokinetic data, and clinical incidence of AMAEs for the selected drugs were collected from reported literature. Extrapolation of literature data was carried-out to obtain exposure data. To determine the drugs muscarinic affinity (Ki values), experiments were performed using 3H-QNB and membrane suspensions of M1, M2, and M3. Cmax, values were combined with Ki values to generate the relevant AMA. Validation of the AMA biomarker was carried-out against the reported AMAEs incidence. Results: With the exclusion of scopolamine and olanzapine for CNS and peripheral AMAEs, respectively, AMA ranking was related to the drugs AMAEs.


© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008