Ionic Effects on Antagonist Binding to the Muscarinic Receptor from Rat Cerebral Cortex

  • B. Hedlund
Part of the Advances in Behavioral Biology book series (ABBI, volume 25)


Studies on the binding of the muscarinic antagonists 3H-N-methyl-4-piperidinyl benzilate (3H-4-NMPB) and 3H-3-quinuclidinyl benzilate (3H-3-QNB) have indicated deviations from first order kinetics of the association reaction under pseudofirst order conditions (8,9). Evidence has been provided for a mechanism of antagonist binding which involves two consecutive equilibria (6). Binding of both benzilates to the muscarinic receptor is followed by an isomerization of the receptor-antagonist complex:
$$ {\text{R}}{\mkern 1mu} {\text{ + }}{\mkern 1mu} {\text{A}}{\mkern 1mu} \mathop \rightleftharpoons \limits_{{{\text{k}}_{{\text{ - 1}}}}}^{{{\text{k}}_{\text{1}}}} {\mkern 1mu} {\text{AR}}{\mkern 1mu} \mathop \rightleftharpoons \limits_{{{\text{k}}_{{\text{ - 2}}}}}^{{{\text{k}}_{\text{2}}}} {\mkern 1mu} {\text{AR*}} $$
where R stands for receptor, A for antagonist, AR and AR* for the two different receptor-antagonist complexes and k1, k−1, k2 and k−2 are rate constants. This mechanism, involving an isomerization reaction, has been proposed for antagonist binding to receptors both in the central nervous system and in the periphery (6). Using 3H-4-NMPB further studies have been carried out for investigation of the ionic effects on the association and dissociation rates and on the equilibrium binding of the 3H-antagonist to the receptor.


Muscarinic Receptor Dissociation Rate Ionic Effect Isomerization Reaction Equilibrium Binding 
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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • B. Hedlund
    • 1
  1. 1.Department of Biochemistry, Arrhenius LaboratoryUniversity of StockholmStockholmSweden

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