Abstract
The cholinolytic activity of the following compounds and their toxicity in mice has been determined: atropine, atropine methylnitrate, 2-diethylaminoethyl cyclopentylhydroxy-(2-thienyl)-acetate (WIN 2299), 1-phenyl-1-cyclo-hexyl-3-piperidino-1-propanol (WIN 511) and the corresponding metho-salts of the last two compounds, WIN 4369 and WIN 1593, respectively.
In barbitalized dogs, the relative order of effectiveness in antagonizing the action of carbachol on blood pressure, salivation and intestinal motility was as follows: WIN 4369 > atropine methylnitrate > atropine sulfate > WIN 1593 > WIN 2299 > WIN 511.
Blockade of pilocarpine-induced salivation in unanesthetized rabbits was obtained with the following order of activity: atropine methylnitrate-800; WIN 4369-320; WIN 1593-130; atropine sulfate-100; WIN 2299-12 and WIN 511-5.
On the isolated rabbit intestine stimulated with acetylcholine, WIN 4369 and WIN 2299 were twice as active as atropine and WIN 1593. Atropine methylnitrate was somewhat more active than atropine.
By instillation into the conjunctival sac of cats, mydriatic activity was as follows: atropine sulfate > WIN 2299 > atropine methylnitrate > WIN 4369 > WIN 511 = WIN 1593.
The negative inotropic effect of acetylcholine on the isolated turtle auricles was reduced or abolished by atropine sulfate and WIN 2299 in about the same concentrations. WIN 4369 and atropine methylnitrate were somewhat less active. WIN 511 was the least active on this preparation.
The central nervous system stimulating effects of the tertiary amines were greater than those of the corresponding quaternary compounds. Atropine and WIN 2299 were the most stimulating.
The nature of the difference in activity between parasympatholytic tertiary amines and the corresponding quaternary ammonium compounds is discussed. It is assumed that the greater activity of the metho-salts is most likely due to a greater specific adsorbability to the receptor and not to the fact that the tertiary amines ionize to a lesser degree.
Footnotes
- Received October 10, 1953.
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