Methoctramine induces nonspecific airway hyperresponsiveness in vivo

• Published in: European journal of pharmacology Vol. 265; no. 1; pp. 67 - 75
• Main Authors: Howell, Ralph E., Kovalsky, Matthew P., Laemont, Keith D.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14.11.1994; Elsevier
• Subjects: Aerosols; airway; Albuterol - administration & dosage; Albuterol - pharmacology; Allergy and immunology; Animals; Arachidonic Acid - metabolism; Atropine - pharmacology; Biological and medical sciences; Bronchial Hyperreactivity - chemically induced; Bronchoconstriction - drug effects; Bronchodilator agent; Diamines - pharmacology; Diamines - toxicity; Drug Synergism; Drug toxicity and drugs side effects treatment; Gallamine Triethiodide - pharmacology; Guinea pig; Guinea Pigs; Histamine - toxicity; Male; Medical sciences; Muscarinic Antagonists; Muscarinic receptor; Ovalbumin - toxicity; Parasympatholytics - pharmacology; Parasympatholytics - toxicity; Pharmacology. Drug treatments; Piperazines - pharmacology; Piperidines - pharmacology; Platelet Activating Factor - toxicity; Propranolol - pharmacology; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Smooth muscle; Toxicity: respiratory system, ent, stomatology; Allergy and immunology; Smooth muscle; Bronchodilator agent; Muscarinic receptor; Guinea pig; airway; Vertebrata; Mammalia; Toxicity; Animal; Bronchodilator; Rodentia; M2 receptor; Antagonist
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)90224-0

We investigated the effects of subtype-selective muscarinic receptor antagonists upon aerosol antigen-induced bronchoconstriction in anesthetized guinea pigs. Neither pirenzepine (muscarinic M 1 receptor-selective), 4-methylpiperidine methiodide (4-DAMP, muscarinic M 3 receptor-selective), [ N-iminomethyl- N′-[(2-hydroxy-2-phenyl-2-cyclohexyl)-ethyl] piperazine HCl (DAC-5945, muscarinic M 3 receptor-selective), ipratropium or atropine inhibited bronchoconstriction, but methoctramine (muscarinic M 2 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 β-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.