Studies on the relationship of binding affinity to psychoactive and anticholingergic potency of a group of psychotomimetic glycolates.
A study was undertaken of the possible relationship of the binding affinity of a series of anticholinergic psychotomimetic drugs to their psychopharmacological and anticholinergic effects. Binding was measured to brain homogenates and nerve endings using [3H]quinuclidinyl benzilate (QB), a highly potent psychotomimetic agent presumably affecting muscarinic sites in the brain. The two stereoisomers of QB were compared; and although the L-isomer had 15 times the binding affinity of D-isomer, the L-isomer had over 200 times the psychopharmacological potency of the D-form. When the relative binding affinity of a homologous series of glycolate esters was compared with their relative psychoacitve potency, the correlation was excellent; however, when compounds with heterocyclic amino rings (e.g., tropanol) other than quinuclidine and piperidine were considered, the correlation was poor. The correlation between binding affinity and antagonism to acetylcholine-induced contraction of ileum was more consistent. A study was undertaken on the effect of added lipids on QB binding to nerve endings, and it was found that phosphatidyl serine had a significant enhancing effect while gangliosides were inhibitory.
D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D006016:Glycolates / Q000378:metabolism / Q000494:pharmacology*; D006213:Hallucinogens / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000032:analysis; D012601:Scopolamine / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D006016:Glycolates; D006213:Hallucinogens; D010276:Parasympatholytics; D010718:Phosphatidylserines; D011812:Quinuclidines; D011955:Receptors, Drug; D001115:Arecoline; D001285:Atropine; D002217:Carbachol; D012601:Scopolamine