Comparative determination of the cardioselectivity of taxine and verapamil in the isolated aorta, atrium and jejunum preparations of rabbits.
The calcium channel antagonistic effect of taxine (CAS 12607-93-1) (active principle of leaves of English yew; Taxus baccata L.) was investigated in isolated aorta of rabbit, and its organ selectivity was determined and compared with that of verapamil (CAS 52-53-9) in isolated aorta, atrium and jejunum preparations of rabbits. Taxine (10(-6)-10(-4) g/ml) inhibited concentration-dependently the Ca(2+)-induced contractions of the aorta depolarized by 60 mmol/l K+ in Ca2+ free media. Both taxine (3 x 10(-7)-10(-4) g/ml) and verapamil (10(-10)-10(-7) g/ml) relaxed the aorta, which was precontracted by 60 mmol/l K+, in a concentration-dependent manner. The IC50 of taxine was 4.78 x 10(-6) and that of verapamil 2.45 x 10(-9) g/ml. Similar effects of taxine were observed in the endothelium-denuded aortic strips. Taxine (3 x 10(-8)-10(-5) g/ml) and verapamil (10(-10)-10(-6) g/ml) produced concentration-dependent negative inotropic and chronotropic effects on isolated atrium preparations. The IC50 values of taxine were 3.63 x 10(-7), and 5.75 x 10(-7) g/ml and those of verapamil 2.69 x 10(-9) and 3.71 x 10(-8) g/ml for contraction and rate, respectively. Taxine and verapamil reduced the amplitude of peristaltic movements of the jejunum. The IC50 values were 1.86 x 10(-5) g/ml for taxine and 3.80 x 10(-8) g/ml for verapamil. From these data it was concluded that taxine has calcium channel antagonistic activity. It was found that taxine was about 13 times more selective for the heart than the vessel and 51 times more selective for the heart than the intestine with respect to inotropic effects, and 8 times more selective for the heart than the vessel, and 32 times more selective for the heart than the intestine in regard to chronotropic effects. When compared with relative selectivity between heart and vessel, taxine is about 14 and 126 times more selective for the heart than verapamil with respect to inotropic and chronotropic effects, and taxine is about 4 and 32 times more selective for the heart than verapamil when compared with relative selectivity on the intestine in regard to inotropic and chronotropic effects, respectively.
Tekol
Y
Y
Department of Pharmacology, Medical Faculty, Erciyes University, Kayseri, Turkey.
Göğüsten
B
B
D000470:Alkaloids / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009928:Organ Specificity; D010936:Plant Extracts / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D043823:Taxoids; D014700:Verapamil / Q000494:pharmacology*
D000470:Alkaloids; D002121:Calcium Channel Blockers; D010936:Plant Extracts; D043823:Taxoids; C047703:taxine; D014700:Verapamil; D011188:Potassium; D002118:Calcium