The binding interactions of Ro 40-5967 at the L-type Ca2+ channel in cardiac tissue

Eur J Pharmacol. 1995 Jul 4;280(2):155-8. doi: 10.1016/0014-2999(95)00194-p.

Abstract

Ro 40-5967 [(1S,2S)-2-[2[3-(2-benzamidopropyl]- methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl- methoxyacetate] is a new Ca2+ channel antagonist active at L-type channels. Radioligand binding studies in cardiac tissue show that Ro 40-5967 does not inhibit 1,4-dihydropyridine binding, but does inhibit diltiazem, desmethoxyverapamil and SR 33557 binding with IC50 values of 8 x 10(-9), 10(-8) and 5 x 10(-8) M, respectively. Equilibrium and kinetic binding studies showed that Ro 40-5967 inhibited both desmethoxyverapamil and SR 33557 binding in an apparently competitive manner. Ro 40-5967 defines an additional and possibly unique antagonist binding site on the L-type voltage-gated Ca2+ channel.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzimidazoles / metabolism*
  • Benzimidazoles / pharmacology
  • Binding, Competitive / drug effects
  • Calcium Channel Blockers / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Heart / drug effects
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Mibefradil
  • Myocardium / metabolism*
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Tetrahydronaphthalenes / metabolism*
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels
  • Tetrahydronaphthalenes
  • Mibefradil