Positive Inotropic Agents

Farah, A.; Alousi, and A A; Schwarz, Richard P.

doi:10.1146/annurev.pa.24.040184.001423

Cited by 87 publications

(32 citation statements)

References 93 publications

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“…Therefore, positive inotropic agents which act by other mechanisms have been considered in recent years (Farah et al, 1984). In the present study we found that YT-1 increased contractile force of rat cardiac tissues concentrationdependently.…”

Section: Discussionsupporting

confidence: 57%

“…Digitalis has other limitations including peripheral vasoconstriction and questionable efficacy during chronic therapy (Mikkelsen et al, 1979). Therefore, many candidates for a digitalis substitute have been developed in recent years (Farah et al, 1984). 2-Phenyl-4-oxo-hydroquinoline (YT-1) is a newly synthesized compound with structure partially similar to quinidine (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Chang

Kuo

1993

British J Pharmacology

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1 The pharmacological and electrophysiological effect of 2-phenyl-4-oxo-hydroquinoline (YT-1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. 2 YT-1 was found to have a positive inotropic effect in both atria and ventricular muscles but did not cause significant increases in the spontaneously beating rate of right atria.3 The positive inotropic effect of YT-1 was antagonized neither by P-nor by a-adrenoceptor antagonists but was partially antagonized by a Ca2" channel blocker (verapamil) and a K+ channel blocker (4-AP). 4 The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT-1 was increased from 3 to 30pM.5 A voltage clamp study revealed that the prolongation of action potential duration by YT-1 was associated with a prominent inhibition of 4-AP-sensitive transient outward current (Ito). At potentials negative to the reversal potential of KI-channels, the inward current through these channels was partially reduced by YT-1. At potentials positive to the reversal potential, the outward current through these channels was affected very little.6 Although YT-1 blocked the amplitude of Ito, the voltage-dependence of the steady-state inactivation of Ito, was unaffected. 7 Apart from the inhibition of K+ currents, YT-1 also inhibited the sodium inward current.8 The evidence suggests that YT-1 increases the slow inward Ca2" current (Ice) significantly.9 It is concluded that the positive inotropic effect of YT-1 is due predominantly to the increase of ICt, and inhibition of Iv,.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Chang

Kuo

1993

British J Pharmacology

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“…Since the occurrence of arrhythmias is deleterious in the treatment ofcardiac failure, the present experiment was set up to examine the effects of OPC-8212 on various types of canine ventricular arrhythmias. The arrhythmia models chosen for the present study were produced by coronary ligation, digitalis intoxication and adrenaline infusion and the effects of were compared with other new positive inotropic agents (Farah et al, 1984), amrinone (Alousi et al, 1979;Endoh et al, 1982) and (Diederen & Kadatz, 1981;Morita et al, 1984;Endoh et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Effects of OPC‐8212, a new positive inotropic agent, on canine ventricular arrhythmias

Hashimoto

Mitsuhashi

1986

British J Pharmacology

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“…In the present study, NA and isoprenaline caused the greatest increase and fastest rate change in atrial tension in the lean, hooded heterozygous group (Fa/fa). Whether these variations in potency of NA and isoprenaline between the strains of rats tested suggests differences in the number of aand/or I3-adrenoceptors on the myocardium, that produce the positive inotropic actions to NA and isoprenaline (Farah et al, 1984), in these groups is only speculation. Carbachol, which has been shown previously (Vadlamudi & McNeill, 1983) to reduce ventricular pressure development in both control and diabetic rat hearts, in this study was more potent, on a molar basis, as a negative inotropic agent on atria isolated from both lean and obese rats than either NA or isoprenaline was at producing positive inotropic effects.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies have shown that gut peptides such as glucagon (Farah et al, 1984) secretin (Chiba, 1976) and vasoactive intestinal peptide (Said et al, 1972) have positive inotropic actions. The present study shows that the endogenous enkephalins ([Met] or [Leul enkephalin) or derivatives (DAMEA and DALEA), peptides known to evoke potent blood pressure changes in conscious rats (Schaz et al, 1980; Thornhill & Saunders, unpublished observations) do Carb -2.0 ± 0.2 -2.7 ± 0.9 -1.9 ± 0.6 NA + ME 3.0 ± 0.4 5.2 ± 0.3 3.6 ± 0.7 Iso + ME [Met] enkephalin on the peripheral vasculature cannot be ruled out (Sander et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

No inotropic action of enkephalins or enkephalin derivatives on electrically‐stimulated atria isolated from lean and obese rats

Saunders¹,

Thornhill²

1985

British J Pharmacology

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3 NA and isoprenaline (l0-7 to 10-6M) caused significant, dose-related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development.[Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 x 10-6M) infused concurrently with NA or isoprenaline (10-6M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone. 4 Carbachol (l0-9 and 10-8M) caused a dose-related decrease (10% and 30-40%, respectively, from pre-injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 x 10-6M) together with carbachol (10-8M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone. 5 The results indicate that the endogenous pentapeptides, ([Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically-stimulated auricles isolated from Sprague-Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo, the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility.

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Positive Inotropic Agents

Cited by 87 publications

References 93 publications

Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Effects of OPC‐8212, a new positive inotropic agent, on canine ventricular arrhythmias

No inotropic action of enkephalins or enkephalin derivatives on electrically‐stimulated atria isolated from lean and obese rats

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