Evaluation of quaternized and neutral muscarinic receptor ligands in normal and DES-treated rat

The localization of quaternized muscarinic receptor (mAChR) antagonists, [11C]methyl tropanyl benzilate ([11C]MTRB) and [11C]methyl quinuclidinyl benzilate ([11C]MQNB), in rat pituitary was compared to that of [11C]tropanyl benzilate ([11C]TRB), a neutral antagonist. The quaternized ligands localize via a mAChR-mediated mechanism as shown by 60% reduction in radioactivity concentrations in the presence of QNB. [11C]TRB appears to localize primarily by a non-mAChR specific mechanism. Induction of pituitary prolactinomas by diethylstilbestrol resulted in a reduction of [11C]MTRB pituitary localization compared to normals. Elevated serum prolactin levels due to prolactinoma presence had no measurable effect on myocardial [11C]MTRB uptake or on KD values. Bmax values for myocardial mAChR were similar for controls and for DES exposure of 10 weeks.