Studies on the relationship of binding affinity to psychoactive and anticholingergic potency of a group of psychotomimetic glycolates

Brain Res. 1977 Mar 25;124(2):331-40. doi: 10.1016/0006-8993(77)90889-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arecoline / pharmacology
  • Atropine / pharmacology
  • Binding Sites
  • Binding, Competitive
  • Brain / drug effects
  • Brain / metabolism*
  • Carbachol / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Dose-Response Relationship, Drug
  • Glycolates / metabolism
  • Glycolates / pharmacology*
  • Hallucinogens / metabolism
  • Hallucinogens / pharmacology*
  • Kinetics
  • Male
  • Parasympatholytics / metabolism
  • Parasympatholytics / pharmacology*
  • Phosphatidylserines / pharmacology
  • Quinuclidines / pharmacology
  • Rats
  • Receptors, Drug / analysis
  • Scopolamine / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Glycolates
  • Hallucinogens
  • Parasympatholytics
  • Phosphatidylserines
  • Quinuclidines
  • Receptors, Drug
  • Arecoline
  • Atropine
  • Carbachol
  • Scopolamine