Activating effects of AR-L 115 BS on the Ca2+ sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle.
2-[(2-Methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS), a new positive inotropic substance, is shown to have direct activating effects upon the Ca2+ sensitive force, stiffness and unloaded shortening velocity of membrane-free, detergent-treated myocardial fibres. At pCa 6.2, application of 7--350 mumol/l AR-L 115 BS (concentrations which are also effective in living papillary muscle) led to a 30-50% increase in force and stiffness and even more in Vmax. A possible intracellular action of the drug on the contractile structures directly is discussed in comparison with the known influences of c-AMP dependent phosphorylation of myocardial regulatory proteins.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D003902:Detergents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects
D002316:Cardiotonic Agents; D003902:Detergents; D007093:Imidazoles; C029758:sulmazole; D002118:Calcium