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.
Howell
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Nova Pharmaceutical Corporation, Baltimore, MD 21224.
Laemont
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Noronha-Blob
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D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D016210:Methacholine Chloride / Q000494:pharmacology; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018727:Muscarinic Antagonists; D010879:Piperazines; D016210:Methacholine Chloride; C070672:DAC 5945; D011433:Propranolol