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Abstract

Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.

J Neumann, T Eschenhagen, I L Grupp, A Haverich, J W Herzig, S Hirt, P Kalmár, W Schmitz, H Scholz, B Stein, H Wenzlaff and N Zimmermann
Journal of Pharmacology and Experimental Therapeutics June 1996, 277 (3) 1579-1585;
J Neumann
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T Eschenhagen
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I L Grupp
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A Haverich
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J W Herzig
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S Hirt
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P Kalmár
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W Schmitz
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H Scholz
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B Stein
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H Wenzlaff
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N Zimmermann
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Abstract

In trabeculae carneae from failing human myocardium, CGP 48506 increased the force of contraction, which reached 310 +/- 41% of predrug values at 100 mumol/l. Its stereoisomer CGP 48508 did not affect the force of contraction (100 mumol/l). The positive inotropic effect of CGP 48506 was not sensitive to 10 mumol/l carbachol. The positive inotropic effect of CGP 48506 was accompanied by increases in time to peak tension and time of relaxation amounting to 175 +/- 4% and 205 +/- 15% of control, respectively, at 100 mumol/l. CGP 48506 but not CGP 48508 sensitized skinned trabeculae from failing human myocardium to calcium with an EC50 value of 10 mumol/l. However, CGP 48506 and CGP 48508 (up to 300 mumol/l) did not affect the activity of PDE isoenzymes I to IV from failing human myocardium. CGP 48506 is the first inotropic agent with calcium-sensitizing properties in the human heart that has been found to be devoid of inhibitory activity on human cardiac PDE isoenzymes.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 277, Issue 3
1 Jun 1996
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Abstract

Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.

J Neumann, T Eschenhagen, I L Grupp, A Haverich, J W Herzig, S Hirt, P Kalmár, W Schmitz, H Scholz, B Stein, H Wenzlaff and N Zimmermann
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1579-1585;

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Abstract

Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.

J Neumann, T Eschenhagen, I L Grupp, A Haverich, J W Herzig, S Hirt, P Kalmár, W Schmitz, H Scholz, B Stein, H Wenzlaff and N Zimmermann
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1579-1585;
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