Pharmacological analysis of cardiac effects of a central cholinergic agent, WEB 1881-FU, in isolated canine heart preparations.
The cardiovascular effects of the novel compound WEB 1881-FU (4-amino-methyl-1-benzyl-pyrrolidine-2-one-fumarate) were investigated using cross-circulated dog atrial preparations. Intravenous injections of WEB 1881 induced a hypotensive effect with slight tachycardia at a large dose in anesthetized dogs. At the same time, it produced slight positive chronotropic and inotropic effects in the isolated atrium perfused with the donor's arterial blood. Direct injections of WEB 1881 into the sinus node artery of the isolated and perfused atrium induced positive chrono- and inotropic effects in a relatively small dose range. At higher doses, it caused biphasic chrono- and inotropic effects, i.e., initial brief negative effects followed by long-lasting positive chrono- and inotropic effects. The negative chrono- and inotropic responses to WEB 1881 were not blocked by atropine in doses which significantly suppressed ACh-induced negative chrono- and inotropic responses. The positive chrono- and inotropic responses to WEB 1881 were significantly inhibited either by a beta-blocker (propranolol) or by an uptake blocker (imipramine). From these results, it is concluded that WEB 1881 has a tyramine-like, catecholamine releasing property. Although a large dose of WEB 1881 has a direct cardiac depressant action, it does not affect muscarinic mechanisms in the heart.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Karasawa
Y
Y
Akahane
K
K
Ren
L M
LM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003427:Cross Circulation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology
D010276:Parasympatholytics; D011760:Pyrrolidinones; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D007099:Imipramine; C056640:nebracetam; D014439:Tyramine