Antagonism of cholinomimetics by troxypyrrolidinium in guinea-pig atria and longitudinal ileal muscle: comparison with hemicholinium-3.
The inhibitory effect of troxypyrrolidinium (trox) (10(-6) to 2 x 10(-3) M) on responses to carbachol (CCh) and acetylcholine (ACh) was investigated in the electrically stimulated left atrium and longitudinal ileal muscle of the guinea pig. In both tissues, trox exhibited antimuscarinic activity causing parallel shifts of the concentration--response curves to both agonists with no depression of maximum responses. Responses to CCh were inhibited by trox (5 x 10(-4) M) to a greater extent than responses to ACh and this difference was maintained following inhibition of cholinesterases with dyflos. In the guinea-pig atrium using CCh as agonist dose ratios produced by the higher concentrations of trox (greater than 5 x 10(-5) M) were less than expected resulting in a non-linear Arunlakshana--Schild (A-S) plot and this effect of trox was maintained in the presence of mecamylamine (2 x 10(-5) M). In longitudinal ileal muscle flattening of the A-S plot with high concentrations of trox did not occur. Although hemicholinium-3 (HC-3) produces a non-linear A-S plot for antimuscarinic activity in atria the A-S plot obtained with the longitudinal ileal strip using HC-3 (2 x 10(-5) to 2 x 10(-3) M) did not exhibit flattening at high concentrations. The dose ratios obtained with HC-3 (5 x 10(-4) M) using CCh as agonist were significantly greater than those obtained with ACh. It is suggested that trox, like HC-3, acts as a metaffinoid antagonist at the muscarinic receptor.
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D010277:Parasympathomimetics / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*
D001565:Benzoates; D002800:Cholinesterase Inhibitors; D010277:Parasympathomimetics; D011759:Pyrrolidines; D006426:Hemicholinium 3; D002802:Cholinesterases