Airway smooth muscle selectivity of the muscarinic antagonist DAC 5945 in vivo

We investigated the M3/M2 antagonist selectivity of [N-iminomethyl-N'-[(2-hydroxy-2-phenyl-2-cyclohexyl)-ethyl] piperazine HCI (DAC 5945) in vivo. ED50 values for reversal of methacholine-induced bronchoconstriction and bradycardia by muscarinic antagonists were determined in anesthetized and ventilated guinea pigs. Atropine, ipratopium, pirenzepine and diphenyl-acetoxy-4-methylpiperidine methiodide (4-DAMP) were non-selective, whereas methoctramine was cardioselective. In contrast, DAC 5945 was a more potent muscarinic antagonist in the airways than in the heart, demonstrating M3/M2 selectivity in vivo.