A new Ca-antagonist, CD-349, binding to the Ca-channel of rat myocardium and brain and hog coronary artery.
The binding to a Ca-channel of a novel 1,4-dihydropyridine (DHP) Ca-antagonist, 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (CD-349), was studied in rat myocardium and brain and hog coronary artery, and the binding was compared with that of other DHPs. In rat myocardium, the binding reaction of [3H]CD-349 was faster than that of nitrendipine (NTD). The association rate constant of [3H]CD-349 was about 10 times higher than that of [3H]NTD. The dissociation rate was also higher than that of [3H]NTD. Scatchard plot analysis of [3H]CD-349 binding showed one high affinity site for CD-349. The dissociation constant (Kd) and maximum number of binding sites (Bmax) were 333 pM and 286 fmoles/mg protein. They were almost the same as those for [3H]NTD. [3H]CD-349 and [3H]NTD bindings were dose dependently inhibited by 1,4-DHPs: nifedipine, nimodipine, nicardipine and CD-349. The order of the inhibitory potency of these drugs was CD-349 greater than nicardipine greater than nimodipine greater than nifedipine, when [3H]CD-349 and [3H]NTD were used as the ligands. Similar results were obtained for rat brain and hog coronary artery. [3H]CD-349 binding was not changed by alpha- or beta-adrenergic, cholinergic, histaminergic or serotonergic agents in rat myocardium. From these results, it is suggested that CD-349 binds to the Ca-channel reversibly with high affinity due to its high association rate for the site.
Muramatsu
M
M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Fujita-Tominaga
A
A
Tanaka
M
M
Ishii
Y
Y
Aihara
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004095:Dihydropyridines / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; C054179:CD 349