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  • Title: Inhibitory effects of TYB 3823, a new antiarrhythmic agent, on mechanical responses in the vascular smooth muscles.
    Author: Shibata S, Satake N, Morikawa M, Kodama I.
    Journal: Gen Pharmacol; 1989; 20(3):303-7. PubMed ID: 2744395.
    Abstract:
    1. TYB 3823 (3 x 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 Ca2+. 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. 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 x 10(-5) M) was not different from that of a single treatment with propranolol (10(-8) M). 4. In rabbit iliac arteries, TYB 3823 (3 x 10(-5) M and 10(-4) M) but not lidocaine (10(-4) M) suppressed the contractile response to caffeine in a Ca2+-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. These results suggested that TYB 3823 may interfere with the responses due to the mobilization of intracellular Ca2+ activated by caffeine and also has both alpha- and beta-adrenoceptor blocking actions on the vascular smooth muscles.
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