ovalbumin and 4-diphenylacetoxy-1-1-dimethylpiperidinium

We investigated the effects of subtype-selective muscarinic receptor antagonists upon aerosol antigen-induced bronchoconstriction in anesthetized guinea pigs. Neither pirenzepine (muscarinic M1 receptor-selective), 4-methylpiperidine methiodide (4-DAMP, muscarinic M3 receptor-selective), [N-iminomethyl-N'-[(2-hydroxy-2-phenyl-2-cyclohexyl)-ethyl] piperazine HCl (DAC-5945, muscarinic M3 receptor-selective), ipratropium or atropine inhibited bronchoconstriction, but methoctramine (muscarinic M2 receptor-selective) produced a dose-dependent increase in bronchoconstriction (up to 46%). Methoctramine also produced increases in bronchoconstriction induced by aerosols of histamine (up to 45%) and platelet activating factor (up to 118%), demonstrating nonspecific airway hyperresponsiveness. This effect of methoctramine was not inhibited by atropine, DAC-5945 or vagotomy and could not be attributed to altered arachidonic acid metabolism or beta-adrenergic antagonism. However, propranolol prevented methoctramine-induced airway hyperresponsiveness, suggesting that this effect resulted from the reported ganglionic blocking activity of methoctramine. In conclusion, muscarinic receptors do not appear to play an important role in antigen-induced bronchoconstriction in anesthetized guinea pigs. Furthermore, caution should be exercised in using methoctramine to characterize the roles of muscarinic receptors in airway inflammatory responses in vivo.

Topics: Aerosols; Albuterol; Animals; Arachidonic Acid; Atropine; Bronchial Hyperreactivity; Bronchoconstriction; Diamines; Drug Synergism; Gallamine Triethiodide; Guinea Pigs; Histamine; Male; Muscarinic Antagonists; Ovalbumin; Parasympatholytics; Piperazines; Piperidines; Platelet Activating Factor; Propranolol; Receptors, Muscarinic