INOTROPIC AND CHRONOTROPIC EFFECTS OF TYLANILINE)-7,8-DIMETHOXY-5H-PYRIMIDO[5,4-B]INDOLE IN GUINEA-PIG ATRIA

Cardiotonic effect of tylaniline)-7,8-dimethoxy-5H-pyrimido[5,4-b]indo le (B-11) was investigated in isolated cardiac tissue preparations. Th e action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrino ne was used for comparison. B-11 produced concentration-dependent (5 x 10(-6)-1 x 10(-4) M) positive inotropic and positive chronotropic res ponses in guinea-pig atrial tissues. The potency of B-11 was greater t han that of amrinone. The cardiotonic effects of B-11 were not modifie d by beta-adrenoceptor blockade. Carbachol inhibited the positive inot ropic effect of B-11. The activity of B-11 was increased in desensitiz ed left atrial tissues. B-11 inhibited the activities of PDE isoenzyme s (type I, II, IV and V) from dog heart ventricle and PDE type IV from guineapig heart ventricle nonselectively. It is concluded that B-11 p ossesses potent positive inotropic activity in guinea-pig atria, and t he effect is probably mediated by a non-selective inhibition of PDE ac tivity.