The binding interactions of Ro 40-5967 at the L-type Ca2+ channel in cardiac tissue.
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.
Rutledge
A
A
School of Pharmacy, State University of New York at Buffalo 14260, USA.
Triggle
D J
DJ
D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D020748:Mibefradil; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000378:metabolism* / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013764:Tetrahydronaphthalenes; D020748:Mibefradil