AF-DX 116 differentiates between prejunctional muscarine receptors located on noradrenergic and cholinergic nerves

Summary Prejunctional affinity constants of the cardioselective muscarine receptor antagonist AF-DX 116 (11-[(2[(diethyl-amino)methyl]-1-piperidinyl)acetyl]-5,11-dihydro6 H-pyrido [2,3-b] [1,4] benzodiazepine-6-one) were determined for muscarine autoreceptors on cholinergic nerves of the guinea-pig ileum and for heteroreceptors on noradrenergic nerves of the rat heart and guinea-pig iris. AF-DX 116 antagonized with low affinity the muscarinic inhibition induced by arecaidine propargyl ester of the stimulation-evoked [³H]acetylcholine overflow (pA₂ 6.74) from the guinea-pig ileum. In contrast, AF-DX 116 was more potent in antagonizing the methacholine-induced inhibition of the stimulation-evoked [³H]noradrenaline overflow from rat heart (pA₂ 7.29) or guinea-pig iris (pA₂ 7.57). The data confirm previously reported differences between prejunctional muscarine heteroreceptors in the rat heart which belong to the cardiac subtype (M₂ or M₂) and autoreceptors in the guinea-pig ileum that cannot be distinguished from the ileal subtype (M₂) or (M₃).Send offprint requests to H. Fuder at the above address