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Related Experiment Videos

Binding studies on two functional cardioselective antimuscarinic compounds.

L K Choo1, F Mitchelson

  • 1School of Pharmacology, Victorian College of Pharmacy, Parkville, Australia.

The Journal of Pharmacy and Pharmacology
|April 1, 1988
PubMed
Summary

Vecuronium and himbacine show functional cardioselectivity at muscarinic receptors but fail to differentiate binding sites. This discrepancy highlights challenges in developing selective muscarinic receptor antagonists.

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Area of Science:

  • Pharmacology
  • Cardiovascular Research
  • Neuroscience

Background:

  • Antimuscarinic compounds like vecuronium and himbacine are used clinically.
  • Functional studies suggest cardioselectivity for these agents at muscarinic receptors.
  • Previous research indicates a discrepancy between functional and binding data for some muscarinic antagonists.

Purpose of the Study:

  • To investigate the binding characteristics of vecuronium and himbacine at cardiac and ileal muscarinic receptors.
  • To reconcile the observed functional cardioselectivity with binding affinities.
  • To understand the basis for the lack of selectivity in binding studies.

Main Methods:

  • Functional assays measuring receptor potency.
  • Radioligand binding studies using [3H](-)-QNB.

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  • Comparison of dissociation constants (Kd) from binding and functional data.

    • Main Results:

    • Vecuronium and himbacine demonstrated 6- and 10-fold higher potency at cardiac versus ileal muscarinic receptors in functional studies.
    • Both compounds failed to differentiate between atrial and ileal muscarinic binding sites in guinea-pig homogenates.
    • Dissociation constants from binding studies were lower than functionally determined values for vecuronium and himbacine.

    Conclusions:

    • Vecuronium and himbacine exhibit functional cardioselectivity but lack selectivity in [3H](-)-QNB binding assays.
    • The basis for this discrepancy between functional and binding data remains unclear.
    • These findings contribute to a growing list of functionally selective muscarinic receptor antagonists that do not show selectivity in binding studies.