Himbacine recognizes a high affinity subtype of M2 muscarinic cholinergic receptors in the rat cerebral cortex

Abstract

The in vitro receptor binding properties of a muscarinic antagonist himbacine have been studied in rat cerebral cortical, cardiac and ileal membranes. Himbacine displayed high affinity (KH = 2.94 nM) for 19%, and low affinity (KL = 71.2 nM) for the remaining muscarinic receptors in rat cerebral cortex. This high affinity of himbacine agrees with its affinity for the 62% of cerebral cortical [3H]AF-DX 116 binding sites (KH = 2.30 nM). The affinity of himbacine for cardiac receptors (Ki = 9.06 nM) and ileal receptors (Ki = 12.4 nM) was the same. Therefore, himbacine appears to be a high-affinity M2-selective ligand which recognizes a subtype of M2 receptors in the cerebral cortex.