Inhibition of platelet adhesion and thrombus formation on a collagen-coated surface by novel carbamoylpiperidine antiplatelet agents.
Inhibition of platelet adhesion and thrombus formation on a collagen-coated surface by novel carbamoylpiperidine antiplatelet agents.
复制标题
新型氨基甲酰哌啶抗血小板药物抑制胶原涂层表面上的血小板粘附和血栓形成。
DOI：
10.1016/0167-4889(92)90148-5
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Lasslo,A
中科院分区：
文献类型：
--
作者：
Alevriadou,BR;McIntire,LV;Lasslo,A
在控制流动条件下，研究了两种新型抗血小板药物1，10-二(N，N-二乙基氨基甲酰基)哌烷二氢溴化物(G-110)和1，6-二[3-(N，N-二乙基氨基甲酰基)哌啶]己烷二氢溴化物(G-112)对血小板在胶原涂层表面的黏附和随后聚集的抑制作用。将涂有牛原纤维I型胶原的玻璃盖片置于平行板灌流室中，将肝素化的人全血与两种氨甲酰哌啶同系物之一的水溶液或等量(1~4μL/毫升血)蒸馏水预先孵育，壁剪切率为10 0 0 S−1。荧光视频显微镜结合显微测量技术被用来可视化和量化从流动的全血到胶原涂层表面的荧光标记的血小板的沉积。在100和200μM浓度下，G-110对血小板聚集的抑制作用为30±9%(±S.E.)2 0 0和4 0 0μM使血小板沉积分别减少19±3%(±SE)和31±2%(±SE)。用数字图像处理技术分析胶原涂层表面血栓生长的动力学。研究发现，这些化合物通过以浓度依赖的方式抑制血栓的表面覆盖率和每个血栓的血小板数量，从而降低血栓生长的速度。这项研究与其他关于相关化合物GT-12、BPAT-117和BPAT-143的研究证实了氨基甲酰哌啶和哌嗪衍生物分子结构中的关键特征的性质，这些特征增强了理想的抗血栓作用，例如两个叔胺(环氮)之间的分子内距离和疏水性水平。
The inhibitory effect of two novel antiplatelet agents, 1,10-bis-(N,N-diethylcarbamoyl)piperidono]decane dihydrobromide (G-110) and 1,6bis[3-(N,N-diethylcarbamoyl)piperidino]hexane dihydrobromide (G-112) on platelet adhesion and subsequent aggregation on collagen-coated surface was evaluated under controlled flow. Glass coverslips coated with bovine fibrillar collagen type I were exposed to heparinized human whole blood that had been preincubated with either aqueous solutions of one of the two carbamoylpiperidine congeners or corresponding amounts (1.0–4.0 μl/ml blood) of distilled water, at a wall shear rate of 1000 s−1, in a parallel-plate perfusion chamber. Epifluorescence video microscopy with a microphotometric measurement technique was used to visualize and quantify deposition of fluorescently-labeled platelets from flowing whole blood onto the collagen-coated surface. At concentrations of 100 and 200 μM, G-110 inhibited platelet accumulation by 30±9% (±S.E.) and 63±3% (±SE), respectively; while G-112 reduced platelet deposition by 19±3% (±SE) and 31±2% (±SE) at concentrations of 200 and 400 μM, respectively. Digital image processing techniques were used to analyze the dynamics of thrombus growth on the collagen-coated surfaces. It was found that the compounds reduced the rate of thrombus growth by impeding both surface coverage and the number of platelets per thrombus in a concentration-dependent manner. This study, together with others on related compounds GT-12, BPAT-117 and BPAT-143, corroborates the nature of pivotal features in the molecular structure of carbamoylpiperidine and nipecotoylpiperazine derivatives which enhance desirable antithrombotic effects, e.g. intramolecular distance between two tertiary amines (ring nitrogens) and levels of hydrophobicity.