Summary
New positive inotropic agents have been synthesized and they are under intensive research to examine whether they are different from older drugs like digitalis and catecholamines in their mechanisms of action and in their clinical effectiveness. Among the positive inotropic agents, those developed by Japanese pharmaceutical laboratories were reviewed mainly in terms of their possible mechanism of action in the cardiac cells. OPC-8212 is orally active and has no chronotropic effect, which may prove beneficial in the treatment of heart failure. It increases intracellular cAMP by PDE inhibition, increases Ca current, and prolongs the duration of action potentials. OPC-8490, with a similar mechanism of action, has vasodilator and positive chronotropic action. MCI-154 is an orally active positive inotropic agent with vasodilator action. The mechanism of action also involves an increase in cAMP, but in addition, sensitization of the contractile elements to Ca has been demonstrated to play a partial role in the inotropic effect. RS-1893, ZSY-27, ZSY-39 and FK664 are orally active positive inotropic agents for which cAMP mechanisms are postulated, but their effectiveness was demonstrated only in experimentally produced heart failure.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Wetzel B, Hauel N (1988) New cardiotonic agents—a promising approach for treatment of heart failure. Trends Pharmacol Sci 9: 166–170
Endoh M, Yanagisawa T, Taira N, Blinks JR (1986) Effects of new inotropic agents on cyclic nucleotide metabolism and calcium transients in canine ventricular muscle. Circulation 73 (Suppl III): 117–133
Kitada Y, Narimatsu A, Matsumura N, Endo M (1987) Increase in Ca++ sensitivity of the contractile system by MCI-154, a novel cardiotonic agent, in chemically skinned fibers from the guinea pig papillary muscles. J Pharmacol Exp Ther 243: 633–638
Taira N (1984) New positive inotropic agents: their modes and mechanisms of action. In: Abe H et al. (eds) Regulation of cardiac function. Japan Sci Soc Press, Tokyo, pp 293–303
Yamashita S, Hosokawa T, Kojima M, Mori T, Yabuuchi Y (1984) In vitro and in vivo studies of 3,4-dihydro-6-[4-(3, 4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H)-quinolinone (OPC-8212), a novel positive inotropic drug, in various animals. Arzneimittel Forschung 34: 342–346
Hori M, Inoue M, Tamai J, Koretsune Y, Kitakaze M, Iwai K, Ito H, Kitabatake A, Kamada T (1986) Cardiotonic activity of a new inotropic agent, 3,4-dihydro-6-[4-(3, 4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H)-quinolinone (OPC-8212), in the dog with and without β-blocker and Ca2++-antagonist pretreatment. Jpn Circ J 50: 37–44
Maruyama Y, Nishioka O, Watanabe J, Keitoku M, Satoh S, Isoyama S, Ashikawa K, Ino-Oka E, Takishima T (1986) Effects of OPC-8212, a new positive inotropic agent, and dobutamine on left ventricular global and ischemic regional functions and coronary hemodynamics under coronary artery stenosis. J Cardiovasc Pharmacol 8: 161–169
Hashimoto K, Yabuuchi Y, Yamashita S, Mori T (1984) Positive inotropic effect of 3, 4-dihydro-6-[4-(3, 4- dimethoxybenoy1)-1-piperazinyl]-2(1H)-quinolinone (OPC-8212) in the dog with experimentally-induced right-sided heart failure. Arzneimittel Forschung 34: 390–393
Hashimoto K, Mitsuhashi H (1986) Effects of OPC-8212, a new positive inotropic agent, on canine ventricular arrhythmias. Br J Pharmacol 88: 915–921
Yanagisawa T, Ishii K, Taira N (1987) Antitachycardic effect of OPC-8212, a novel cardiotonic agent, on tachycardiac responses of guinea pig isolated right atria to isoproterenol and histamine. J Cardiovasc Pharmacol 10: 47–54
Mori T, Yamashita S, Hosokawa T, Yabuuchi Y (1988) Cardiovascular effects of OPC-8490, a new positive inotropic agent with vasodilator action, (abstract) Jpn J Pharmacol 46: 130P
Narimatsu A, Kitada Y, Satoh N, Suzuki R, Okushima (1987) Cardiovascular pharmacology of 6-[4-(4′-pyridy1) aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a novel and potent cardiotonic agent with vasodilator properties. Arzneimittel Forschung 37: 398–406
Hosono M, Taira N (1987) Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations. J Cardiovasc Pharmacol 10: 692–698
Kitada Y, Narimatsu A, Suzuki R, Endoh M, Taira N (1987) Does the positive inotropic action of a novel cardiotonic agent, MCI-154, involve mechanisms other than cyclic AMP? J Pharmacol Exp Ther 243: 639–645
Miyake S, Shiga H, Koike H, Mizuno H, Yorikane R, Oda T, Iijima Y, Kumakura S, Morisawa Y (1988) Cardiovascular pharmacology of RS-1893, an orally active cardiotonic agent with arterial and venous vasodilator actions. Jpn J Pharmacol 47: 273–283
Shiga H, Miyake S, Koike H (1988) Echocardiographic study of cardiotonic effects of RS-1893 in conscious beagles with congestive heart failure. (abstract) Jpn J Pharmacol 47: 215P
Chiba S, Furukawa Y, Saegusa K, Ogiwara Y (1986) Cardiovascular effects of ZSY-27 [5-methyl-6-(4-pyridiny1)-2H-1, 4-thiazine-3(4H)-one-hydrochloridel] in the dog cross-circulated atrial preparation. Jpn Heart J 27: 749–757
Tanaka H, Tajimi K, Kasai T, Kobayashi K, Nakamura K, Okuaki A (1987) Cardiovascular effects of ZSY-27 in dogs with pentobarbital-induced heart failure. Circulation Control 8 (Supp1): 274–275
Tajimi K, Tanaka H, Kasai T, Kobayashi K, Okuaki A (1989) Selective pulmonary vasodilatory effect of ZSY-27 in dogs with pulmonary hypertension due to pulmonary embolism. Circ Care Med 17: 163–165
Esumi K, Sudo Y, Ozaki T, Maeda K, Ono T (1988) Effect of FK664, a new cardioprotective agent, on acutely induced congestive heart failure in anesthetized dogs (abstract) FASEB J 2: A1817
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Tokyo
About this chapter
Cite this chapter
Hashimoto, K. (1989). New Inotropic Agents for Treatment of Heart Failure. In: Hori, M., Suga, H., Baan, J., Yellin, E.L. (eds) Cardiac Mechanics and Function in the Normal and Diseased Heart. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67957-8_34
Download citation
DOI: https://doi.org/10.1007/978-4-431-67957-8_34
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-68020-8
Online ISBN: 978-4-431-67957-8
eBook Packages: Springer Book Archive