Effect of a new antiarrhythmic BK 129 on canine vascular smooth muscle in vitro.
The effect of a new carbanilate derivative BK 129, 1-methoxymethyl-2(1-perhydroazepinyl)ethyl ester 2-(n)-pentyloxycarbanilic acid hydrochloride, was tested on preparations of canine dorsal pedal and coronary artery in vitro. The drug produced relaxation of arterial rings both under resting conditions and under precontraction with KCl. BK 129, at a concentration of 10(-5) mol/l, produced a shift to the right of the concentration-response curve of phenylephrine, with a decrease in the slope and a depression of the maximal response. BK 129 inhibited the response to norepinephrine and blocked histamine- and norepinephrine-induced contractions in Ca(2+)-free physiological salt solution. The electrical stimulation-induced contractions of arterial preparation were also inhibited. BK 129 shifted the concentration-response curve of CaCl2 in Ca(2+)-free depolarizing solution to the right in a non-competitive manner. It may be concluded that BK 129 is a local anesthetic which possesses relaxant properties. It appears to inhibit Ca2+ entry into the smooth muscle cell and Ca2+ release from sarcoplasmic reticulum.
Sotníková
R
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Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, CSFR.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011955:Receptors, Drug / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001381:Azepines; D011955:Receptors, Drug; C089290:BK 129