Kirsten R, Breidert M, Sparwasser K, Ochs J G, Hesse K, Nelson K
Abteilung Klinische Pharmakologie, Universitätsklinikum Frankfurt/M, Germany.
Int J Clin Pharmacol Ther. 1995 Feb;33(2):76-80.
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.
在体外和体内研究了新型抗高血压药物DA2激动剂卡莫昔罗对人血小板聚集的影响。在一项开放性研究中，15例原发性高血压患者在经过2周的安慰剂期后，接受3种剂量的卡莫昔罗，即每日0.5、1和2毫克，每种剂量服用2周。在每个2周疗程结束时，测量血压、血小板聚集、血浆卡莫昔罗和血浆儿茶酚胺。体外初步实验表明，10微摩尔的卡莫昔罗可使肾上腺素诱导的聚集速度降低10%：增加卡莫昔罗浓度会导致剂量依赖性抑制，在1毫摩尔时完全抑制。卡莫昔罗本身在体外对人血小板有微弱的聚集作用。口服0.5、1和2毫克卡莫昔罗2周后，血压分别从治疗前的163±11/103±3毫米汞柱降至155±11/97±4、148±11/93±4和143±11/90±6毫米汞柱。最后一次服用胶囊2个半小时后，血浆卡莫昔罗水平在服用0.5、1和2毫克卡莫昔罗后分别为0.37±0.612、0.95±1.045和3.69±2.570纳克/毫升。未发现卡莫昔罗对血浆儿茶酚胺有影响。与治疗前的100%相比，体外5-羟色胺诱导的血小板聚集速度在服用0.5、1和2毫克卡莫昔罗后分别降至70%、38%和69%。肾上腺素诱导的聚集速度也以同样的方式降低。这些结果表明，卡莫昔罗是一种具有抗血栓形成潜力的抗高血压药物。
