CARMOXIROLE INHIBITS PLATELET-AGGREGATION IN-VITRO AND EX-VIVO

The influence of carmoxirole, a new antihypertensive DA(2)-agonist on human platelet aggregation was studied in vitro and ex vivo. In an ope n study 15 patients with essential hypertension received 3 doses of ca rmoxirole, 0.5, 1 and 2 mg daily, each for a 2-week period, following a 2-week placebo phase. At the end of each 2-week period blood pressur e, platelet aggregation, plasma carmoxirole and plasma catecholamines were measured. Preliminary experiments in vitro showed that 10 mu M ca rmoxirole inhibited the adrenaline induced aggregation velocity by 10% . Increasing the carmoxirole concentration caused dose dependent inhib ition which was complete at 1 mM. Carmoxirole itself caused a weak agg regating effect on human platelets in vitro. Blood pressure was reduce d from 163 +/- 11/103 +/- 3 before treatment to 155 +/- 11/97 +/- 4, 1 48 +/- 11/93 +/- 4 and 143 +/- 11/90 +/- 6 mmHg following 2 weeks of 0 .5, 1 and 2 mg oral carmoxirole, respectively. Carmoxirole plasma leve ls 2 1/2 h after the last capsule administration were 0.37 +/- 0.612, 0.95 +/- 1.045 and 3.69 +/- 2.570 ng/ml following treatment with 0.5, 1 and 2 mg carmoxirole, respectively. No influence of carmoxirole on p lasma catecholamines could be established. Compared to 100% before tre atment, the 5-hydroxytryptamine induced platelet aggregation velocity ex vivo decreased to 70%, 38% and 69% after the administration of 0.5, 1 and 2 mg carmoxirole, respectively. The adrenaline induced aggregat ion velocity was reduced in the same manner. These results show that c armoxirole is an antihypertensive agent with antithrombotic potential.