Inflammatory activity of polymeric photoproducts of chlorpromazine

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.