Belliard A M, Leroy C, Banide H, Farinotti R, Lacour B
Laboratoire de Pharmacie Clinique-Physiologie, UPRES 2706, Faculté de Pharmacie, 92296, Châtenay-Malabry Cedex, France.
Exp Parasitol. 2003 Jan-Feb;103(1-2):51-6. doi: 10.1016/s0014-4894(03)00070-5.
Drugs currently available for visceral leishmaniasis treatment are potentially toxic, have to be administered by parenteral route and frequently give rise to drug resistance, due to the involvement of P-glycoproteins (P-gp) in Leishmania. The purpose of this study was to investigate a possible inhibitory effect of 2n-propylquinoline (2nPQ) on P-gp activity. 2nPQ is a new oral anti-leishmanial drug that has demonstrated its efficacy in BALB/c infected mice with Leishmania donovani [Antimicrob. Agents Chemother. 37 (1993) 859]. Rat everted gut sacs and human intestinal Caco-2 cell lines were used to study the effect of 2nPQ on P-gp activity. Our results demonstrate an inhibitory effect of 2nPQ on the P-gp activity with two P-gp substrates (rhodamine 123 and digoxin), two P-gp inhibitors (cyclosporin A and verapamil), and in two different species. Alone or associated with other active drugs, 2nPQ would be very useful to control Leishmania Multi-Drug-Resistance and intestinal P-gp in humans with kala-azar.
目前可用于治疗内脏利什曼病的药物具有潜在毒性，必须通过肠胃外途径给药，并且由于利什曼原虫中存在P-糖蛋白（P-gp），这些药物经常会产生耐药性。本研究的目的是调查2-正丙基喹啉（2nPQ）对P-gp活性可能的抑制作用。2nPQ是一种新型口服抗利什曼病药物，已在感染杜氏利什曼原虫的BALB/c小鼠中证明了其疗效[《抗菌药物化疗》37（1993）859]。使用大鼠外翻肠囊和人肠道Caco-2细胞系来研究2nPQ对P-gp活性的影响。我们的结果表明，2nPQ对两种P-gp底物（罗丹明B和地高辛）、两种P-gp抑制剂（环孢菌素A和维拉帕米）以及在两个不同物种中均具有P-gp活性抑制作用。单独使用或与其他活性药物联合使用时，2nPQ对于控制内脏利什曼病患者的利什曼原虫多重耐药性和肠道P-gp将非常有用。
