An attempt to reduce the photosensitizing potential of chlorpromazine with the simultaneous use of beta- and dimethyl-beta-cyclodextrins in guinea pigs.
The effects of topically applied beta-cyclodextrin (beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) on photoallergic contact dermatitis due to chlorpromazine hydrochloride (CPZ) were investigated using the photomaximization technique in guinea pigs. From the gross and histological observations, the photosensitizing potential of CPZ with the simultaneous topical use of beta-CyDs was significantly lower than that of CPZ alone. The alleviating efficacy of DM-beta-CyD was greater than that of beta-CyD. beta-CyDs suppressed the penetration of CPZ into the skin through the formation of poorly skin-permeable complexes. In addition, beta-CyDs inhibited (a) the photoinduced free radicals derived from CPZ in the isolated dry skin and (b) the in vitro photochemical binding of CPZ to bovine serum albumin. These observations suggest that beta-CyDs suppress the photochemical reactions between CPZ and biological macromolecules present in the skin, resulting in the failure to form a photoantigen. The present results indicate that DM-beta-CyD is particularly effective in alleviating photoallergic contact dermatitis due to CPZ.
Hoshino
T
T
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Ishida
K
K
Irie
T
T
Uekama
K
K
Ono
T
T
D000818:Animals; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects*; D003505:Cyclodextrins / Q000008:administration & dosage*; D003912:Dextrins / Q000008:administration & dosage*; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006168:Guinea Pigs; D010787:Photosensitivity Disorders / Q000473:pathology / Q000517:prevention & control*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013056:Spectrophotometry, Ultraviolet; D013213:Starch / Q000008:administration & dosage*
D003505:Cyclodextrins; D003912:Dextrins; D013213:Starch; D002746:Chlorpromazine