Guanylpirenzepine Distinguishes Between Neuronal m1 and m4 Muscarinic Receptor Subtypes

Abstract

Guanylpirenzepine, a polar, non-quaternary analog of pirenzepine, exhibited a novel binding behavior in rat brain regions: in competition binding experiments against [³H]pirenzepine labeling the M₁ receptor in membranes from cerebral cortex, hippocampus and striatum, the compound, differently from pirenzepine, displayed heterogeneous binding curves. Computer assisted analysis of these curves, evidenced the existence of two populations of binding sites: a large proportion (84–89%) of high affinity receptors (K_H = 64–92 nM) and a remainder with very low affinity (K_L = 19–28 μM). Like pirenzepine, quanylpirenzepine showed low affinity for the glandular M₃ and the cardiac M₂ receptors when [³H]N-methylscopolamine was used to label the receptors in membranes from these two tissues; affinity values for guanylpirenzepine were 1336 and 5790 nM respectively, vs 323 and 683 nM for pirenzepine. We conclude that guanylpirenzepine is able to discriminate between m1 and m4 receptor subtypes and may represent a new tool for deeper studies on mascarinic receptors classification.