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具有正性肌力作用的二氢吡啶类药物Bay K 8644不影响去表皮心肌纤维的钙敏感性或钙释放。

The positive inotropic dihydropyridine Bay K 8644 does not affect calcium sensitivity or calcium release of skinned cardiac fibres.

作者信息

Thomas G, Gross R, Pfitzer G, Rüegg J C

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):378-81. doi: 10.1007/BF00692904.

DOI:10.1007/BF00692904
PMID:2581146
Abstract

BAY K 8644 is a positive inotropic dihydropyridine which concentration-dependently increased contractile force in guinea-pig atria at 10 to 1000 nmol/l. In chemically skinned cardiac fibres from guinea-pig hearts the substance did not change the tension induced by calcium. Also BAY K 8644 did not release calcium from intracellular myocardial stores like caffeine since it failed to evoke a contractile response in saponin-treated, calcium-loaded cardiac muscle. Thus, the drug exerts its effects neither by sensitizing the contractile apparatus to calcium nor by a caffeine-like action.

摘要

BAY K 8644是一种具有正性肌力作用的二氢吡啶，在10至1000纳摩尔/升浓度范围内，可使豚鼠心房收缩力呈浓度依赖性增加。在豚鼠心脏的化学去表皮心肌纤维中，该物质不会改变由钙诱导的张力。此外，BAY K 8644不像咖啡因那样从细胞内心肌储存中释放钙，因为它在经皂角苷处理且加载钙的心肌中未能引发收缩反应。因此，该药物既不是通过使收缩装置对钙敏感，也不是通过类似咖啡因的作用来发挥其效应。

相似文献

1
The positive inotropic dihydropyridine Bay K 8644 does not affect calcium sensitivity or calcium release of skinned cardiac fibres.具有正性肌力作用的二氢吡啶类药物Bay K 8644不影响去表皮心肌纤维的钙敏感性或钙释放。
Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):378-81. doi: 10.1007/BF00692904.
2
A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent.一种二氢吡啶（Bay k 8644），可增强豚鼠和小牛心肌细胞中的钙电流。一种新型的正性肌力药物。
Circ Res. 1985 Jan;56(1):87-96. doi: 10.1161/01.res.56.1.87.
3
Stimulation frequency alters the inotropic response of atrial muscle to BAY K-8644.刺激频率会改变心房肌对BAY K - 8644的变力反应。
Eur J Pharmacol. 1985 Jan 2;107(2):209-14. doi: 10.1016/0014-2999(85)90060-3.
4
Calcium agonism, a new mechanism for positive inotropy. Hemodynamic effects and mode of action of BAY K 8644.钙激动作用，一种正性肌力的新机制。BAY K 8644的血流动力学效应及作用方式。
Adv Myocardiol. 1985;6:59-70.
5
The positive inotropic action of the nifedipine analogue, Bay K 8644, in guinea-pig and rat isolated cardiac preparations.硝苯地平类似物Bay K 8644对豚鼠和大鼠离体心脏标本的正性肌力作用。
Br J Pharmacol. 1985 Sep;86(1):27-32. doi: 10.1111/j.1476-5381.1985.tb09431.x.
6
Positive inotropic effects of the calcium channel activator Bay K 8644 on guinea-pig and human isolated myocardium.钙通道激活剂Bay K 8644对豚鼠和人离体心肌的正性肌力作用。
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):85-92. doi: 10.1007/BF00169482.
7
Vascular and cardiac effects of a new dihydropyridine derivative, YC-170: a comparison with Bay K 8644.新型二氢吡啶衍生物YC-170对血管和心脏的作用：与Bay K 8644的比较
J Pharmacol Exp Ther. 1986 Aug;238(2):670-8.
8
Effects of BAY K-8644 on inotropic and arrhythmogenic actions of digoxin.BAY K-8644对地高辛变力作用和致心律失常作用的影响。
Eur J Pharmacol. 1986 May 13;124(1-2):11-20. doi: 10.1016/0014-2999(86)90119-6.
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Antagonism between (-)-N6-phenylisopropyladenosine and the calcium channel facilitator Bay K 8644, on guinea-pig isolated atria.（-）-N6-苯基异丙基腺苷与钙通道促进剂Bay K 8644对豚鼠离体心房的拮抗作用。
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10
Differential antagonism by Bay k 8644, a dihydropyridine calcium agonist, of the negative inotropic effects of nifedipine, verapamil, diltiazem and manganese ions in canine ventricular muscle.二氢吡啶类钙激动剂Bay k 8644对硝苯地平、维拉帕米、地尔硫䓬和锰离子在犬心室肌中负性肌力作用的差异性拮抗作用。
Br J Pharmacol. 1985 Feb;84(2):577-84. doi: 10.1111/j.1476-5381.1985.tb12943.x.

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Steady-state [Ca2+]i-force relationship in intact twitching cardiac muscle: direct evidence for modulation by isoproterenol and EMD 53998.完整的抽搐心肌中稳态[Ca2+]i-张力关系：异丙肾上腺素和EMD 53998调节的直接证据。
Biophys J. 1995 Jul;69(1):189-201. doi: 10.1016/S0006-3495(95)79889-7.
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Ca-agonists: a new class of inotropic drugs.钙激动剂：一类新型的正性肌力药物。
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Effects of caffeine and ryanodine on depression of post-rest tension development produced by Bay K 8644 in canine ventricular muscle.

本文引用的文献

1
Activating effects of AR-L 115 BS on the Ca2+ sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle.AR-L 115 BS对哺乳动物心肌离体收缩结构中Ca2+敏感力、硬度和无负荷缩短速度（Vmax）的激活作用。
Arzneimittelforschung. 1981;31(1a):188-91.
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Effects of Ca antagonist on the contractile force in glycerinated dog heart muscles.钙拮抗剂对甘油处理的犬心肌收缩力的影响。
Pflugers Arch. 1982 Oct;395(1):49-54. doi: 10.1007/BF00584967.
3
Effect of calcium-antagonist and calmodulin-antagonist drugs on calmodulin-dependent contractions of chemically skinned vascular smooth muscle from rabbit renal arteries.
咖啡因和兰尼碱对Bay K 8644所致犬心室肌静息后张力发展抑制的影响。
Br J Pharmacol. 1989 Aug;97(4):1279-91. doi: 10.1111/j.1476-5381.1989.tb12590.x.
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Effect of Bay K8644 on cytosolic calcium transients and contraction in embryonic cardiac ventricular myocytes.Bay K8644对胚胎心室肌细胞胞质钙瞬变和收缩的影响。
Pflugers Arch. 1989 Jan;413(3):225-33. doi: 10.1007/BF00583534.
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Impairment of Ca release from mammalian ventricular sarcoplasmic reticulum by the calcium channel agonist Bay K 8644.钙通道激动剂Bay K 8644对哺乳动物心室肌浆网钙释放的损害。
Br J Pharmacol. 1988 Jun;94(2):291-2. doi: 10.1111/j.1476-5381.1988.tb11529.x.
6
Positive inotropic effects of the calcium channel activator Bay K 8644 on guinea-pig and human isolated myocardium.钙通道激活剂Bay K 8644对豚鼠和人离体心肌的正性肌力作用。
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):85-92. doi: 10.1007/BF00169482.
7
The effects of the cardiotonic dihydropyridine derivatives Bay k 8644 and H160/51 on post-rest adaptation of guinea-pig papillary muscles.强心二氢吡啶衍生物Bay k 8644和H160/51对豚鼠乳头肌静息后适应性的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):488-95. doi: 10.1007/BF00569391.
钙拮抗剂和钙调蛋白拮抗剂药物对兔肾动脉化学去膜血管平滑肌钙调蛋白依赖性收缩的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):85-9. doi: 10.1007/BF00634253.
4
Influence of Ca++-channel blocking agents on calcium transients and tension development in isolated mammalian heart muscle.钙离子通道阻滞剂对离体哺乳动物心肌钙瞬变和张力发展的影响。
Circ Res. 1983 Feb;52(2 Pt 2):I47-52.
5
Cyclic AMP inhibits contractility of detergent treated glycerol extracted cardiac muscle.环磷酸腺苷抑制经去污剂处理的甘油提取心肌的收缩性。
Pflugers Arch. 1981 Sep;391(3):208-12. doi: 10.1007/BF00596172.
6
Binding properties of a novel calcium channel activating dihydropyridine in monolayer cultures of beating myocytes.新型钙通道激活二氢吡啶在搏动心肌细胞单层培养物中的结合特性
FEBS Lett. 1984 Feb 13;167(1):88-92. doi: 10.1016/0014-5793(84)80838-8.
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Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels.通过激活Ca2+通道具有正性肌力作用的新型二氢吡啶类化合物。
Nature. 1983;303(5917):535-7. doi: 10.1038/303535a0.
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[Electromechanical uncoupling of vascular smooth muscle as the basic principle of coronary dilatation by 4-(2'-nitrophenyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (BAY a 1040, Nifedipine). 1. The significance of Ca ++ ions for the bioelectrical and mechanical activity of smooth muscle].[血管平滑肌的机电解偶联作为4-(2'-硝基苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸二甲酯（BAY a 1040，硝苯地平）冠脉扩张的基本原理。1. Ca++离子对平滑肌生物电和机械活动的意义]
Arzneimittelforschung. 1972 Feb;22(2):334-44.
9
Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium.硝苯地平对哺乳动物心室肌慢内向电流的抑制作用。
Naunyn Schmiedebergs Arch Pharmacol. 1977 Jul;298(3):267-72. doi: 10.1007/BF00500899.
10
Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells.由单个去表皮心肌细胞肌浆网中钙触发的钙释放所诱导的收缩。
J Physiol. 1975 Aug;249(3):469-95. doi: 10.1113/jphysiol.1975.sp011026.