Interaction of DPI 201-106 with cardiac muscarinic receptors.
The effects of the new cardiotonic compound, DPI 201-106, on muscarinic responses and muscarinic receptor binding were studied in the guinea pig heart. DPI 201-106 exerted a pronounced anticholinergic action in isolated auricles and a moderate one in papillary muscles, which resembled the pattern of a functional antagonism. However, in competition binding experiments, DPI 201-106 inhibited binding of the specific muscarinic antagonist [3H]NMS with equal potency in atrial and ventricular homogenates (apparent KI = 0.7 mumol/l in atria and 1.2 mumol/l in ventricles). At higher concentrations (greater than 3 mumol/l), DPI 201-106 slowed the dissociation of [3H]NMS from cardiac muscarinic receptors, indicating that DPI 201-106 affects in addition a site allosteric to the muscarinic receptor. It is concluded that DPI 201-106 is able to inhibit cholinergic responses in the heart, not only by a functional antagonism but also by direct interaction with muscarinic receptors.
Groschner
K
K
Institut für Pharmakodynamik und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Ulle
P
P
Brunner
F
F
Kukovetz
W R
WR
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D010879:Piperazines; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; C046261:DPI 201-106