title: Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacie Clinique-Physiologie, UPRES 2706, Faculté de Pharmacie, 92296, Châtenay-Malabry Cedex, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Belliard
authors.forename: C
authors.initials: C
authors.lastname: Leroy
authors.forename: H
authors.initials: H
authors.lastname: Banide
authors.forename: R
authors.initials: R
authors.lastname: Farinotti
authors.forename: B
authors.initials: B
authors.lastname: Lacour
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004077:Digoxin / Q000378:metabolism; D004351:Drug Resistance; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020112:Rhodamine 123 / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: C116019:2-propylquinoline; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000981:Antiprotozoal Agents; D005456:Fluorescent Dyes; D011804:Quinolines; D020112:Rhodamine 123; D004077:Digoxin; D016572:Cyclosporine; D014700:Verapamil