Electrophysiologic effects of saterinone and milrinone in the isolated guinea pig myocardium.
The positive inotropic agent milrinone and the newly synthesized compound saterinone [+/-)-1,2-dihydro-5-[4-[2-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl] propoxy]phenyl]-6-methyl-2-oxo-3-pyridine-carbonitrile, BDF 8634) dose-dependently increased the contractile force of guinea pig left atria. During a 90-min exposure, 10(-4) mol/l saterinone caused a continuous increase of the functional refractory period (FRP), while the initial positive inotropic effect faded gradually. No change of the FRP was observed with milrinone. Saterinone (10(-4) mol/l) also increased the action potential duration and the FRP of guinea pig papillary muscles, while milrinone had no influence on either parameter. Both milrinone and saterinone increased the amplitude, depolarization velocity and duration of slow response action potentials in K+-depolarized muscles. These effects appeared in the presence of tetrodotoxin or propranolol and could be reversed by carbachol. It is concluded that saterinone increases the force of contraction and the slow inward current by inhibiting cardiac phosphodiesterase. The increase of the FRP may be attributed to a decrease of the membrane K+ conductance.
Iven
H
H
Department of Pharmacology, Medical University, Lübeck, Fed. Rep. of Germany.
Brasch
H
H
Armah
B I
BI
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D020105:Milrinone; D010210:Papillary Muscles / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011728:Pyridones; D013779:Tetrodotoxin; D011433:Propranolol; D020105:Milrinone; C058572:saterinone