Iseki K, Sugawara M, Saitoh H, Miyazaki K, Arita T
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
J Pharm Pharmacol. 1988 Oct;40(10):701-5. doi: 10.1111/j.2042-7158.1988.tb06998.x.
The effect of chlorpromazine on the membrane permeability of beta-lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D-glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25 degrees C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D-glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of beta-lactam antibiotics and actively transported substances in a different manner.
使用大鼠小肠刷状缘膜囊泡研究了氯丙嗪对β-内酰胺类抗生素（苄青霉素、氨苄青霉素、头孢拉定和头孢氨苄）以及主动转运物质（甘氨酰甘氨酸和D-葡萄糖）膜通透性的影响。除头孢氨苄外，在氯丙嗪存在下，这些抗生素在25℃时的初始摄取量显著增加。相反，甘氨酰甘氨酸和D-葡萄糖的转运受到显著抑制。这些结果表明，药物和主动转运物质这两组具有不同的渗透过程。还研究了氯丙嗪浓度对膜脂质流动性的影响，通过1,6-二苯基-1,3,5-己三烯（DPH）和1-苯胺基-8-萘磺酸盐（ANS）的荧光偏振来评估。ANS的荧光偏振随着氯丙嗪浓度的增加而降低，而DPH的荧光偏振增加，这表明膜表面流动性的增加可能以不同方式影响β-内酰胺类抗生素和主动转运物质的渗透。
