Interaction of chlorpromazine, fluphenazine and trifluoperazine with ocular and synthetic melanin in vitro
Interaction of chlorpromazine, fluphenazine and trifluoperazine with ocular and synthetic melanin in vitro
复制标题
DOI：
10.1691/ph.2008.7663
复制
发表时间：
2008-05-01
期刊：
影响因子：
1.6
通讯作者：
Orzechowska, A.
中科院分区：
文献类型：
--
作者：
Buszman, E.;Beberok, A.;Orzechowska, A.
本研究的目的是在体外检查三种吩噻嗪衍生物氯丙嗪、氟奋乃静和三氟拉嗪（对眼睛结构造成不利影响）与从猪眼中分离出的天然黑色素以及用作模型聚合物的合成多巴黑色素的结合能力。通过紫外分光光度法测定与黑色素结合的药物量。药物-黑色素复合物形成动力学结果分析表明，随着初始药物浓度的增加和孵育时间的延长，与黑色素结合的药物量增加，约24小时后达到平衡状态。结合参数，即结合位点的数量 (n) 和缔合常数 (K)，是根据斯卡查德图确定的。对于精神抑制药-眼部黑色素和精神抑制药-多巴-黑色素复合物，发现了两类独立的结合位点，对于氯丙嗪和氟奋乃静复合物，关联常数K-1类似于10(4)，K-2类似于10(2)M-1，对于三氟拉嗪复合物，K-1类似于10(5)，K-2类似于10(3)M-1。强 (n(1)) 和弱 (n(2)) 结合位点的数量表明，与多巴黑色素相比，所检测的药物对眼部黑色素的亲和力较低。讨论了氯丙嗪、氟奋乃静和三氟拉嗪在体外与黑色素（尤其是眼部黑色素）相互作用的能力以及这些药物在体内的眼部毒性。
The aim of this study was to examine in vitro the binding capacity of three phenothiazine derivatives chlorpromazine, fluphenazine and trifluoperazine - causing adverse effects in the eye structures, to natural melanin isolated from pig eyes as well as to synthetic DOPA-melanin used as a model polymer. The amount of drug bound to melanin was determined by UV spectrophotometry. The analysis of results for the kinetics of drug-melanin complex formation showed that the amount of drug bound to melanin increases with increasing initial drug concentration and longer incubation time, attaining an equilibrium state after about 24 h. Binding parameters, i.e. the number of binding sites (n) and association constants (K), were determined on the basis of Scatchard plots. For neuroleptic-ocular melanin and neuroleptic-DOPA-melanin complexes two classes of independent binding sites were found, with association constants K-1 similar to 10(4) and K-2 similar to 10(2) M-1 for chlorpromazine and fluphenazine complexes, and K-1 similar to 10(5) and K-2 similar to 10(3) M-1 for trifluoperazine complexes. The numbers of strong (n(1)) and weak (n(2)) binding sites indicate lower affinity of the drugs examined to ocular melanin compared with DOPA-melanin. The ability of chlorpromazine, fluphenazine and trifluoperazine to interact with melanin, especially the ocular melanin, in vitro is discussed in relation to the ocular toxicity of these drugs in vivo.