Actions of some esters of 3,3-dimethylbutan-1-ol (the carbon analogue of choline) on the guinea-pig ileum.
1 Estimates were made of the affinity constants for postganglionic acetylcholine receptors of the guinea-pig ileum of the esters of 3,3-dimethylbutan-1-ol with benzilic, (+/-)-cyclohexylphenylglycollic, (+/-)-mandelic, and diphenylacetic acids.2 Attempts were made to check the competitive nature of the antagonism by using as wide a range of concentrations of antagonist as possible, consistent with their limited solubility, and by testing some of the compunds in the presence of a known competitive antagonist.3 By comparing the affinities with those of the corresponding quaternary nitrogen compounds, the contribution made by the positive charge in the onium group to the binding by receptors may be assessed and has been found to be variable. The carbon analogue of benziloylcholine has about one-tenth of its affinity, that of (+/-)-cyclohexylphenylglycolloylcholine has only about one-sixtieth of its affinity, but that of (+/-)-mandelylcholine has slightly higher affinity than that of (+/-)-mandelylcholine itself.4 3,3-Dimethylbutylacetate appeared to be a partial agonist with an affinity constant of about 2.6 x 10(3). The contribution made by the positive charge to the binding of acetylcholine at these receptors therefore seems likely to lie within the range observed with antagonists and there is no reason to believe that there is necessarily greater intimacy of association by agonists than by antagonists.5 Although the C-C and /#/N-C bonds in -CMe(3) and -/#/NMe(3) are similar in length, the groups do not occupy the same volume in solution in water.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001561:Benzilates / Q000138:chemical synthesis / Q000494:pharmacology; D001667:Binding, Competitive; D000440:Butanols / Q000138:chemical synthesis / Q000494:pharmacology*; D002794:Choline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004158:Diphenylacetic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004952:Esters; D006016:Glycolates / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008333:Mandelic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009994:Osmolar Concentration; D011950:Receptors, Cholinergic; D013329:Structure-Activity Relationship
D001561:Benzilates; D000440:Butanols; D004158:Diphenylacetic Acids; D004952:Esters; D006016:Glycolates; D008333:Mandelic Acids; D011950:Receptors, Cholinergic; D002794:Choline; D000109:Acetylcholine