Buszman Ewa, Rózańska Renata
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland.
Acta Pol Pharm. 2003 Jul-Aug;60(4):257-61.
The aim of this study was to examine in vitro the binding capacity of thioridazine to natural melanin isolated from pig eyes and to synthetic DOPA-melanin. The amount of drug bound to melanin was determined by the use of the UV spectrophotometric method. Studies on the kinetics of thioridazine-melanin complex formation showed that the amount of drug bound to melanin increases with increasing initial drug concentration and the prolongation or incubation time, allowed to attain equilibrium state after about 24 hours. Binding parameters, i.e., the number of independent binding sites and the association constants were determined on the basis of Scatchard plots. For thioridazine-ocular melanin and thioridazine-DOPA-melanin complexes two classes of binding sites were found with the association constants K1 approximately 2 x 10(4) M(-1) and K2 approximately 9 x 10(2) M(-1). For ocular and synthetic melanin complexes with thioridazine no significant differences in the values of binding parameters were found. The demonstrated ability of thioridazine to interact with melanin in vitro is discussed in relation to this drug ocular toxicity in vivo.
本研究的目的是在体外检测硫利达嗪与从猪眼中分离出的天然黑色素以及合成的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。硫利达嗪 - 黑色素复合物形成动力学研究表明，与黑色素结合的药物量随初始药物浓度的增加以及孵育时间的延长而增加，约24小时后达到平衡状态。基于Scatchard图确定结合参数，即独立结合位点的数量和缔合常数。对于硫利达嗪 - 眼黑色素和硫利达嗪 - 多巴黑色素复合物，发现两类结合位点，缔合常数K1约为2×10⁴ M⁻¹，K2约为9×10² M⁻¹。对于硫利达嗪与眼黑色素和合成黑色素的复合物，未发现结合参数值有显著差异。结合硫利达嗪在体内的眼毒性，讨论了其在体外与黑色素相互作用的能力。
