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

Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy-5H-pyrimido[5,4-b]indole (B-11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison. B-11 produced concentration-dependent (5 x 10(-6)-1 x 10(-4) M) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B-11 was greater than that of amrinone. The cardiotonic effects of B-11 were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B-11. The activity of B-11 was increased in desensitized left atrial tissues. B-11 inhibited the activities of PDE isoenzymes (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 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.