INVITRO AND EXVIVO CA-ANTAGONISTIC EFFECT OF 2-METHOXYETHYL(E)-3-PHENYL-2-PROPEN-1-YL(+/-)-1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)PYRIDINE-3,5-DICARBOXYLATE (FRC-8653), A NEW DIHYDROPYRIDINE DERIVATIVE

被引：16

作者：

HOSONO, M ^{[1
]}

IIDA, H ^{[1
]}

IKEDA, K ^{[1
]}

HAYASHI, Y ^{[1
]}

DOHMOTO, H ^{[1
]}

HASHIGUCHI, Y ^{[1
]}

YAMAMOTO, H ^{[1
]}

WATANABE, N ^{[1
]}

YOSHIMOTO, R ^{[1
]}

机构：

[1] AJINOMOTO CO INC,CENT RES LABS,LIFE SCI LABS,TOTSUKA KU,YOKOHAMA 244,JAPAN

来源：

JOURNAL OF PHARMACOBIO-DYNAMICS | 1992年 / 15卷 / 10期

关键词：

2-METHOXYETHYL(E)-3-PHENYL-2-PROPEN-1-YL(+/-)-1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)PYRIDINE-3,5-DICARBOXYLATE (FRC-8653); DIHYDROPYRIDINE; CALCIUM-ANTAGONISM; VASORELAXING EFFECT; FURA-2; H-3-NITRENDIPINE BINDING;

D O I：

10.1248/bpb1978.15.547

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The characteristics of calcium antagonism and vascular effect of 2-methoxyethyl(E)-3-phenyl-2-propen-1-yl(+/-)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8653) were investigated. FRC-8653 inhibited an increase in intracellular free calcium concentration during membrane depolarization in PC12 cells. FRC-8653 also inhibited the specific binding of H-3-nitrendipine to cardiac membranes, in a similar manner to nifedipine and nicardipine. FRC-8653 inhibited KCl- and CaCl2-induced contractions in isolated rabbit aorta, but failed to affect norepinephrine-induced contraction. The vasorelaxing effect of FRC-8653 in rabbit aorta developed more slowly than those of nifedipine and nicardipine. In ex vivo experiment, the inhibitory effect of orally administered FRC-8653 against KCl-contraction in rat aorta lasted longer than that of nifedipine. These findings suggest that FRC-8653 dilates blood vessels by blocking calcium influx via dihydropyridine-sensitive, voltage-dependent calcium channels and that the vascular effects are slow in development and long in duration.

引用

页码：547 / 553

页数：7

共 12 条

[1]

BOLGER GT, 1983, J PHARMACOL EXP THER, V225, P291

[2] CALCIUM-CHANNEL BLOCKING PROPERTIES OF AMLODIPINE IN VASCULAR SMOOTH-MUSCLE AND CARDIAC-MUSCLE INVITRO - EVIDENCE FOR VOLTAGE MODULATION OF VASCULAR DIHYDROPYRIDINE RECEPTORS [J].

BURGES, RA ;

GARDINER, DG ;

GWILT, M ;

HIGGINS, AJ ;

BLACKBURN, KJ ;

CAMPBELL, SF ;

CROSS, PE ;

STUBBS, JK .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1987, 9 (01) :110-119

[3] SPECIFIC PHARMACOLOGY OF CALCIUM IN MYOCARDIUM, CARDIAC-PACEMAKERS, AND VASCULAR SMOOTH-MUSCLE [J].

FLECKENSTEIN, A .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1977, 17 :149-166

[4]

GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3400

[5]

IKEDA K, IN PRESS OYO YAKURI

[6] DUAL ACTION OF FRC8653, A NOVEL DIHYDROPYRIDINE DERIVATIVE, ON THE BA-2+ CURRENT RECORDED FROM THE RABBIT BASILAR ARTERY [J].

OIKE, M ;

INOUE, Y ;

KITAMURA, K ;

KURIYAMA, H .

CIRCULATION RESEARCH, 1990, 67 (04) :993-1006

[7]

PAN M, 1983, PHARMACOLOGIST, V25, P202

[8] PURIFICATION OF THE CARDIAC 1,4-DIHYDROPYRIDINE RECEPTOR CALCIUM-CHANNEL COMPLEX [J].

RENGASAMY, A ;

PTASIENSKI, J ;

HOSEY, MM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 126 (01) :1-7

[9]

RHODES DG, 1985, MOL PHARMACOL, V27, P612

[10]

TRIGGLE DJ, 1987, ANNU REV PHARMACOL, V27, P347

← 1 2 →