Lack of cardiostimulant effects of bamifylline in in vitro and in vivo models.
The cardiac effects of bamifylline (Bamifix), an alkylxanthine derivative, were evaluated on in vivo and in vitro cardiac preparations and compared with those of theophylline and enprofylline. In isolated rat and guinea-pig right atria bamifylline, in contrast to the other xanthines, left the rate of contraction unchanged or reduced it. In isolated rat and guinea-pig left atria the compound induced only slight inotropic effects showing an intrinsic activity significantly lower than that of theophylline and enprofylline. In isolated rabbit papillary muscles bamifylline administration was without effect up to 10(-3) mol/l and decreased the contractile force at a higher concentration, while theophylline dose-dependently increased inotropism. Also in anaesthetized rabbits intravenous administration of bamifylline produced negative chronotropic and dromotropic effects that were associated, at the highest dose, with a reduction of myocardial contractility. Theophylline and enprofylline, at the same equimolar doses, induced positive chronotropic and inotropic effects. The results show that bamifylline is devoid of cardiostimulant effects in respect to other xanthine derivatives. Moreover, they suggest that bamifylline acts on cardiac muscle by a mechanism, probably linked to the Ca+(+)-movements across the cardiac membrane, able to outweigh the effects due to its antiphosphodiesterase activity.
Bongrani
S
S
Pharmacological Department, Chiesi Farmaceutici S.p.A., Parma, Italy.
Razzetti
R
R
Papotti
M
M
Pastore
F
F
Bergamaschi
M
M
D000818:Animals; D002316:Cardiotonic Agents; D004562:Electrocardiography; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013045:Species Specificity; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D002316:Cardiotonic Agents; D014970:Xanthines; D012110:Reserpine; D013806:Theophylline; C034347:enprofylline; C006683:bamifylline