Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis.

A M Belliard; C Leroy; H Banide; R Farinotti; B Lacour

doi:10.1016/s0014-4894(03)00070-5

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PubMed · 12810046

Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis.

A M Belliard·C Leroy·H Banide·R Farinotti·B Lacour

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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.

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ATP Binding Cassette Transporter, Subfamily B, Member 1 Animals Antiprotozoal Agents Caco-2 Cells Cyclosporine Digoxin Drug Resistance Fluorescent Dyes Humans Ileum In Vitro Techniques Leishmaniasis, Visceral Male Quinolines Rats Rats, Sprague-Dawley Rhodamine 123 Verapamil Journal Article

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A M Belliard, C Leroy, H Banide, R Farinotti, B Lacour. Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis.. https://doi.org/10.1016/s0014-4894(03)00070-5

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