We wished to provide comparative information regarding the direct effects of
flosequinan, a novel
quinolone under development for treating
heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--
milrinone,
ouabain,
captopril and
diltiazem--that have been used to treat
heart failure patients, as well as for
flosequinoxan, which is the primary metabolite of
flosequinan.
Flosequinan produced a potent and balanced relaxant effect on
norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations,
flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with
flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with
flosequinan and
flosequinoxan in the following ways:
Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations;
ouabain produced both
vasoconstrictor and positive inotropic effects;
diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and
captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of
flosequinan and
flosequinoxan is unique as compared with that of other agents that have been used to treat patients with
heart failure.