PT  - JOURNAL ARTICLE
AU  - J Neumann
AU  - T Eschenhagen
AU  - I L Grupp
AU  - A Haverich
AU  - J W Herzig
AU  - S Hirt
AU  - P Kalmár
AU  - W Schmitz
AU  - H Scholz
AU  - B Stein
AU  - H Wenzlaff
AU  - N Zimmermann
TI  - Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.
DP  - 1996 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1579--1585
VI  - 277
IP  - 3
4099  - http://jpet.aspetjournals.org/content/277/3/1579.short
4100  - http://jpet.aspetjournals.org/content/277/3/1579.full
SO  - J Pharmacol Exp Ther1996 Jun 01; 277
AB  - 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.