Studies on Muscarinic Binding Sites in Human Brain Identified with [³H]Pirenzepine

Abstract: Pirenzepine, a potent antimuscarinic agent with apparent selectivity for a subtype (M₁) of muscarinic receptors, was used in tritiated form to characterize its binding to human brain tissue. Specific [³H]pirenzepine binding showed rapid association and dissociation. From kinetic and competitive binding experiments, its K_D was 5.5 nM and 9 nM, respectively. Regional distribution of [³H]pirenzepine binding determined in parallel with [³H]quinuclidinyl benzilate binding, a nonselective muscarinic antagonist, indicated a significant correlation for the maximum number of binding sites for the two radioligands in 13 brain regions, with the highest amount of binding for each in the putamen and the least in the cerebellum. Binding for [³H]pirenzepine averaged 57% of that for [³H]quinuclidinyl benzilate, with a range of 20% (cerebellum) to 77% (frontal cortex). Most antidepressants and neuroleptics tested had affinities for [³H]pirenzepine binding sites that were not significantly different from their previously reported values obtained with the use of [³H]quinuclidinyl benzilate.