PDF(Pubmed)
Abstract：
\"Purple Drank\", a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [N-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective.
摘要：
\"紫色饮料\",含有异丙嗪（PMZ）和可待因（COD）的软饮料，因其致幻作用而受到全球欢迎。消耗大量这种组合可能导致潜在的致命事件。这些药物与血浆蛋白的结合可以通过增加药物相互作用的风险来加剧这一问题，副作用,和/或毒性。在这里，PMZ及其主要代谢产物[N-去甲基异丙嗪（DMPMZ）和异丙嗪亚砜（PMZSO）]与人血清白蛋白（HSA）的结合亲和力，和COD一起,通过区域方法通过高效亲和层析(HPAC)进行了研究。PMZ及其代谢物对HSA表现出显著的结合亲和力(%b值高于80%),而COD表现出65%的%b值。为了辨别这些化合物所结合的HSA的特定位点，使用华法林和（S）-布洛芬作为位点I和II的探针进行置换实验，分别,这表明所有分析物都与这两个位点结合。分子对接研究证实了实验结果，加强从经验数据中获得的见解。计算机数据还表明，PMZ及其代谢产物与COD之间的竞争可能发生在HSA的两个位置，但主要是在第二站点。由于目标化合物是手性的，还探索了HSA结合的对映选择性，显示这些化合物的结合不是对映选择性的。
