Rutledge A, Triggle D J
School of Pharmacy, State University of New York at Buffalo 14260, USA.
Eur J Pharmacol. 1995 Jul 4;280(2):155-8. doi: 10.1016/0014-2999(95)00194-p.
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.
Ro 40-5967 [（1S，2S）-2-[2-[3-（2-苯甲酰胺基丙基）-甲基氨基]乙基]-6-氟-1,2,3,4-四氢-1-异丙基-2-萘基-甲氧基乙酸酯]是一种对L型通道有活性的新型钙通道拮抗剂。在心脏组织中的放射性配体结合研究表明，Ro 40-5967不抑制1,4-二氢吡啶结合，但确实抑制地尔硫卓、去甲氧基维拉帕米和SR 33557结合，其IC50值分别为8×10^(-9)、10^(-8)和5×10^(-8)M。平衡和动力学结合研究表明，Ro 40-5967以明显竞争性方式抑制去甲氧基维拉帕米和SR 33557结合。Ro 40-5967在L型电压门控钙通道上定义了一个额外的且可能独特的拮抗剂结合位点。
