Pharmacological profiles of YM-16151-1 and its optical isomers: a novel calcium entry blocking and selective beta-1 adrenoceptor blocking agent
Asano, M; Uchida, W; Shibasaki, K; Terai, M; Inagaki, O; Takenaka, T; Matsumoto, Y; Fujikura, T
| HERO ID | 4851235 |
|---|---|
| In Press | No |
| Year | 1990 |
| Title | Pharmacological profiles of YM-16151-1 and its optical isomers: a novel calcium entry blocking and selective beta-1 adrenoceptor blocking agent |
| Authors | Asano, M; Uchida, W; Shibasaki, K; Terai, M; Inagaki, O; Takenaka, T; Matsumoto, Y; Fujikura, T |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 254 |
| Issue | 1 |
| Page Numbers | 204-211 |
| Abstract | The pharmacological properties of YM-16151-1 [(+/-)-dimethyl 4-[2-[4-(2-hydroxy-3-phenoxypropylamino)butoxyl]-5-nitrop hen yl]-2,6- dimethyl-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride] and its optical isomers were evaluated in in vitro studies and radioligand binding assay. In isolated tissues, YM-16151-1 produced a competitive antagonism of CaCl2-induced contraction in the isolated rabbit aorta with a pKca-1 value of 8.17, and also produced a competitive antagonism of isoproterenol-induced positive chronotropic responses in the isolated rat atria with a pA2 value of 8.47. In rat brain membrane preparations, YM-16151-1 produced dose-dependent inhibitions of [3H]nitrendipine and [3H]dihydroalprenolol bindings with pKi values of 7.21 and 8.07, respectively. Calcium entry blocking activity of YM-16151-1 was 7 times weaker and 3 times greater than nifedipine and diltiazem, respectively. Beta-1 adrenoceptor blocking activity of YM-16151-1 was 2 times weaker than that of propranolol. YM-16151-1 showed about 900-fold selectivity for beta-1 adrenoceptor. YM-16151-1 also showed a weak alpha-1 adrenoceptor blocking activity and its potency was about 13 times weaker than that of phentolamine. S-(-)- and R-(+)-isomers of YM-16151-1 showed the same potency of calcium entry blocking activity. However, in beta-1 adrenoceptor blocking activity, the S-(-)-enantiomer was about 13 to 22 times more potent than the R-(+)-enantiomer. Oral administration of YM-16151-1 produced a dose-dependent blood pressure lowering effect without increasing heart rate in conscious spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Pmid | 1973196 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |