A new vasodilator 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) has a dual mechanism of action on platelet aggregation.

3-Isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404) at a concentration of greater than or equal to 4.34 X 10(-5) M inhibited adenosine diphosphate-, arachidonic acid- and collagen-induced aggregation of rabbit platelets. In rabbit, KC-404 (0.5 and 2 mg/kg, i.v.) caused a decrease in weight of collagen strip extracorporeally superfused with arterial blood, because of a disaggregation of deposited platelet aggregates. This disaggregatory effect of KC-404 was markedly diminished by the pretreatment of animals with aspirin. KC-404 (greater than or equal to 4.34 X 10(-6) M) and its major metabolite diOH-KD-404 (greater than or equal to 3.78 X 10(-7) M) significantly potentiated the anti-aggregatory action of prostacyclin on rabbit platelets. KC-404 (greater than or equal to (4.34 X 10(-8) M) exerted a similar effect in rat platelets. KC-404 had no significant effect on 6-keto-PGF1 alpha and thromboxane A2 formation by rat aortic segment and rabbit platelets, respectively. KC-404 inhibited cyclic AMP phosphodiesterase (Ki = 91 microM). The present results indicate that KC-404 exhibits its anti-platelet effect via the inhibition of cyclic AMP phosphodiesterase activity in platelets and via the potentiation of anti-aggregatory activity of prostacyclin on platelets.