RT Journal Article
SR Electronic
T1 Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1579
OP 1585
VO 277
IS 3
A1 Neumann, J
A1 Eschenhagen, T
A1 Grupp, I L
A1 Haverich, A
A1 Herzig, J W
A1 Hirt, S
A1 Kalmár, P
A1 Schmitz, W
A1 Scholz, H
A1 Stein, B
A1 Wenzlaff, H
A1 Zimmermann, N
YR 1996
UL http://jpet.aspetjournals.org/content/277/3/1579.abstract
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.