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第二代抗精神病药物和典型的神经阻滞剂对体外胶原蛋白诱导的血小板聚集的影响。

The effects of the second generation antipsychotics and a typical neuroleptic on collagen-induced platelet aggregation in vitro.

机构信息

Department of Affective and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.

出版信息

World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):293-9. doi: 10.1080/15622970903144020.

Abstract

OBJECTIVE

Antipsychotics are widely used in psychiatry, and consequently a lot of their side effects have been reported. One of them is cardiovascular disease leading to increased risk of stroke, thrombosis, pulmonary, embolism, in which hyperactivation of blood platelets is involved. The purpose of the present study was to examine the effects of the second generation antipsychotics (SGAs) such as clozapine, risperidone, and olanzapine, and a typical neuroleptic - haloperidol - on the one step of platelet activation-platelet aggregation induced by collagen in vitro. Blood was collected into buffered sodium citrate (3.8%) and centrifuged to get platelet-rich plasma (PRP). In PRP (2x10(8) platelets/ml) obtained from healthy volunteers that was incubated with antipsychotics (clozapine, risperidone, olanzapine, haloperidol; 30 min) aggregation of blood platelets was measured using a Chrono-Log Lumi-aggregometer. Aggregation of platelets was measured after stimulation of platelets with 1 microl of collagen (2 microg/ml).

RESULTS

Clozapine, like haloperidol reduced platelet aggregation induced by collagen (inhibition of platelet aggregation reached about 20%) (P=1x10(-5) and P=0.003, respectively). Risperidone had also a weak antiaggregatory effect (P=0.05). Among tested antipsychotics only olanzapine had no effect on collagen-stimulated platelet aggregation (P>0.05).

CONCLUSION

The obtained results indicate that the difference in action of tested drugs on platelet aggregation may dependent on the various chemical structures of these drugs. Clozapine, risperidone and haloperidol are structurally diverse, and they all significantly reduce platelet aggregability induced by collagen. On the other hand, a close structural analog of clozapine - olanzapine - did not inhibit platelet aggregation. However, mechanism of antipsychotics action on blood platelets is not clear. Moreover, it seems that clozapine, risperidone and haloperidol treatment due to antiaggregatory action may have even some antithrombotic effects.

摘要

目的

抗精神病药在精神病学中被广泛应用,因此已经报道了很多其副作用。其中之一是心血管疾病,导致中风、血栓形成、肺栓塞等风险增加,其中血小板的过度激活起了作用。本研究的目的是研究第二代抗精神病药(SGAs),如氯氮平、利培酮和奥氮平,以及一种典型的神经阻滞剂——氟哌啶醇,对体外胶原诱导的血小板活化——血小板聚集的一步的影响。将血液收集到缓冲的柠檬酸钠(3.8%)中,然后离心得到富含血小板的血浆(PRP)。从健康志愿者中获得的 PRP(2x10(8)个血小板/ml)与抗精神病药(氯氮平、利培酮、奥氮平、氟哌啶醇;30 分钟)孵育后,使用 Chrono-Log Lumi-aggregometer 测量血小板聚集。用 1 微升胶原(2 微克/ml)刺激血小板后测量血小板聚集。

结果

氯氮平与氟哌啶醇一样,可降低胶原诱导的血小板聚集(血小板聚集抑制率约为 20%)(P=1x10(-5)和 P=0.003)。利培酮也有较弱的抗聚集作用(P=0.05)。在所测试的抗精神病药中,只有奥氮平对胶原刺激的血小板聚集没有影响(P>0.05)。

结论

所得到的结果表明,测试药物对血小板聚集的作用差异可能取决于这些药物的各种化学结构。氯氮平、利培酮和氟哌啶醇在结构上有所不同,它们都能显著降低胶原诱导的血小板聚集。另一方面,氯氮平的紧密结构类似物——奥氮平——没有抑制血小板聚集。然而,抗精神病药对血小板的作用机制尚不清楚。此外,氯氮平、利培酮和氟哌啶醇由于抗聚集作用,似乎对血液有抗血栓作用。

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