Shigehara N, Kakegawa H, Miyataka H, Matsumoto H, Isobe A, Satoh T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Biol Pharm Bull. 1993 Jun;16(6):576-8. doi: 10.1248/bpb.16.576.
To confirm the inflammatory activity of polymeric photoproducts (CPZ-polymers) of chlorpromazine (CPZ), which were obtained by gel filtration of a UV-pre-irradiated CPZ aqueous solution, the histamine release from rat peritoneal exudate cells was studied and the paw-inflammation in mice induced by these CPZ-polymers was examined. CPZ-polymers induced a dose-dependent histamine release at concentrations of 1, 3 and 10 mg/ml. This effect was approximately one-tenth of that of compound 48/80. Furthermore, CPZ-polymers markedly induced lasting paw-edema in a dose-dependent manner, the swellings remaining for at least 96 h. When intraperitoneally injected into mice, CPZ-polymers induced a significant elevation of histamine release in the peritoneal cavity 0.5 h after the injection, compared with a control group. The histamine levels in the cavities returned to normal within the next 0.5 h, and remained normal for at least 23 h, indicating that histamine release may be caused only in the early stages of CPZ-polymer-induced inflammation. The inflammatory activity of the CPZ-polymers suggests that they are inflammatory substances formed from CPZ by UV-irradiation.
为了证实通过对紫外线预照射的氯丙嗪（CPZ）水溶液进行凝胶过滤得到的氯丙嗪聚合物光产物（CPZ - 聚合物）的炎症活性，研究了大鼠腹腔渗出细胞的组胺释放情况，并检测了这些CPZ - 聚合物诱导的小鼠爪部炎症。CPZ - 聚合物在浓度为1、3和10mg/ml时诱导出剂量依赖性的组胺释放。这种效应约为化合物48/80的十分之一。此外，CPZ - 聚合物以剂量依赖性方式显著诱导持续的爪部水肿，肿胀至少持续96小时。当腹腔注射到小鼠体内时，与对照组相比，CPZ - 聚合物在注射后0.5小时诱导腹腔内组胺释放显著升高。腹腔内组胺水平在接下来的0.5小时内恢复正常，并至少23小时保持正常，这表明组胺释放可能仅在CPZ - 聚合物诱导炎症的早期阶段发生。CPZ - 聚合物的炎症活性表明它们是由CPZ通过紫外线照射形成的炎症物质。
