title: Interaction of the cardiotonic agent DPI 201-106 with cardiac Ca2+ channels.
abstract: The cardiotonic agent DPI 201-106 was investigated for its effects on (a) contractile force in guinea pig left atria, (b) membrane currents in isolated guinea pig cardiac myocytes, and (c) [3H]nitrendipine binding in guinea pig cardiac membranes. The compound elicited a positive inotropic effect in normally polarized (5.9 mM extracellular KCl) and a negative inotropic effect in partially depolarized (20 mM KCl) isolated, electrically stimulated left atria. This decrease in contractile force was probably caused by inactivation of the fast Na+ inward current and concomitant blockade of the inward Ca2+ current. The blocking effect on Ca2+ channels was directly shown in voltage-clamp experiments using isolated cardiocytes. Further evidence for interaction of DPI 201-106 with Ca2+ channels was obtained from the [3H]nitrendipine binding studies. Thus, Ca2+ antagonism contributes to the complex pharmacologic profile of DPI 201-106, and is probably responsible for the bradycardia and lowering of systemic vascular resistance observed in vivo.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay
chemical_list: D002316:Cardiotonic Agents; D007473:Ion Channels; D010879:Piperazines; C046261:DPI 201-106; D009543:Nifedipine; D002118:Calcium