Pancuronium and gallamine are antagonists for pre- and post-junctional muscarinic receptors in the guinea-pig lung.
The effects of atropine, pancuronium and gallamine were tested on pre- and post-junctional muscarinic receptors in the lung. Inhibition of bronchoconstriction induced by intravenous injection of acetylcholine (ACh) was used as a measure of post-junctional receptor blockade. All three antagonists reduced ACh-induced bronchoconstriction. The effects were dose-related for atropine and pancuronium and complete inhibition was obtained with 0.01 mg/kg and 10 mg/kg respectively. Gallamine was much less potent than the other two drugs; the inhibitory effect was not dose-related and never exceeded 50% even at a dose of 10 mg/kg. In contrast, blockade of pre-junctional inhibitory muscarinic receptors in pulmonary parasympathetic nerves by these three antagonists, produced potentiation of bronchoconstriction induced by vagal-nerve stimulation. Consequently, the effect of the three antagonists on vagally-induced bronchoconstriction is dependent on the balance between their pre- and post-junctional blocking activity. Gallamine was the most effective and atropine the least effective antagonist for potentiating nerve-induced bronchoconstriction. At doses which produce 100% neuromuscular blockade, both pancuronium (0.04 mg/kg) and gallamine (4 mg/kg) potentiated vagally-induced bronchoconstriction. At these doses, pancuronium doubled and gallamine caused a four-fold increase in vagally-induced bronchoconstriction, despite partial concurrent blockade of muscarinic receptors in the smooth muscle of the airways.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000294:innervation*; D008297:Male; D010197:Pancuronium / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000502:physiology; D010276:Parasympatholytics; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D001285:Atropine; D010197:Pancuronium; D000109:Acetylcholine; D005703:Gallamine Triethiodide