Carmoxirole inhibits platelet aggregation in vitro and ex vivo.
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.
Kirsten
R
R
Abteilung Klinische Pharmakologie, Universitätsklinikum Frankfurt/M, Germany.
Breidert
M
M
Sparwasser
K
K
Ochs
J G
JG
Hesse
K
K
Nelson
K
K
D001794:Blood Pressure / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood; D066298:In Vitro Techniques; D007211:Indoles / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology*; D011725:Pyridines / Q000097:blood / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology
D018491:Dopamine Agonists; D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D012701:Serotonin; C071485:carmoxirole; D004837:Epinephrine