The influence of
carmoxirole, a new
antihypertensive DA2-agonist on human platelet aggregation was studied in vitro and ex vivo. In an open study 15 patients with
essential hypertension received 3 doses of
carmoxirole, 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 pressure, platelet aggregation, plasma
carmoxirole and plasma
catecholamines were measured. Preliminary experiments in vitro showed that 10 microM
carmoxirole inhibited the
adrenaline induced aggregation velocity by 10%: Increasing the
carmoxirole concentration caused dose dependent inhibition which was complete at 1 mM.
Carmoxirole itself caused a weak aggregating effect on human platelets in vitro. Blood pressure was reduced from 163 +/- 11/103 +/- 3 before treatment to 155 +/- 11/97 +/- 4, 148 +/- 11/93 +/- 4 and 143 +/- 11/90 +/- 6 mmHg following 2 weeks of 0.5, 1 and 2 mg oral
carmoxirole, respectively.
Carmoxirole plasma levels 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 plasma
catecholamines could be established. Compared to 100% before treatment, 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 aggregation velocity was reduced in the same manner. These results show that
carmoxirole is an
antihypertensive agent with antithrombotic potential.