Inhibitory effects of TYB 3823, a new antiarrhythmic agent, on mechanical responses in the vascular smooth muscles

Abstract 1. 1. TYB 3823 (3 × 10 −5 M to 10 −3 M) but not lidocaine (10 −4 M) inhibited the contractile response to norepinephrine in rabbit aorta in a competitive manner. On the other hand, TYB 3823 had no effect on contractile responses to histamine, 5-hydroxytryptamine, high KCl and Ca 2+ . 2. 2. In rabbit aorta, TYB 3823 (10 −5 M and 10 −4 M) but not lidocaine (10 −4 M) also antagonized the ouabain-induced contraction and this action was less potent than that of phentolamine (10 −6 M). 3. 3. In rabbit coronary arteries precontracted with KCl (40 mM), either TYB 3823 or lidocaine inhibited the isoproterenol-induced relaxation to the same levels. Propranolol at 10 −8 M shifted the relaxation curve for isoproterenol to the right and at 10 −6 M it almost completely prevented the relaxation. Further, the effect of a combined treatment with propranolol (10 −8 M) and TYB 3823 (3 × 10 −5 M) was not different from that of a single treatment with propranolol (10 −8 M). 4. 4. In rabbit iliac arteries, TYB 3823 (3 × 10 −5 M and 10 −4 M) but not lidocaine (10 −4 M) suppressed the contractile response to caffeine in a Ca 2+ -free medium with EGTA and nifedipine. Nitroglycerin (10 −4 M) also inhibited the response but this action was less potent than that of TYB 3823. The combined treatment of the tissue with TYB 3823 and nitroglycerin (both 10 −4 M) further inhibited the responses to caffeine as compared to a single treatment with each drug. 5. 5. These results suggested that TYB 3823 may interfere with the responses due to the mobilization of intracellular Ca 2+ activated by caffeine and also has both α- and β-adrenoceptor blocking actions on the vascular smooth muscles.