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Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection

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dc.contributor.author Mukherjee, S.
dc.contributor.author Mukherjee, B.
dc.contributor.author Mukhopadhyay, R.
dc.contributor.author Naskar, K.
dc.contributor.author Sundar, S.
dc.contributor.author Dujardin, J. C.
dc.contributor.author Das, A. K.
dc.contributor.author Roy, S.
dc.date.accessioned 2013-03-08T15:19:19Z
dc.date.available 2013-03-08T15:19:19Z
dc.date.issued 2012
dc.identifier.issn 1935-2727
dc.identifier.doi http://dx.doi.org/10.1371/journal.pntd.0001987
dc.identifier.other ITG-B6A
dc.identifier.other DBM
dc.identifier.other U-MOLPAR
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other Abstract
dc.identifier.other UPD54
dc.identifier.uri http://hdl.handle.net/10390/7361
dc.description.abstract BACKGROUND: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD) promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF alpha, IFN gamma and iNOS activity increased with the concomitant decrease in IL 10 and TGF beta level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. CONCLUSIONS: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar. en
dc.language English en
dc.subject Protozoal diseases en
dc.subject Kala azar en
dc.subject Visceral en
dc.subject Leishmaniasis en
dc.subject Leishmania donovani en
dc.subject Vectors en
dc.subject Sandflies en
dc.subject Phlebotomus argentipes en
dc.subject Treatment en
dc.subject Drug development en
dc.subject Monotherapy en
dc.subject Oral en
dc.subject Affordability en
dc.subject Imipramine en
dc.subject Drug resistance en
dc.subject Promastigotes en
dc.subject Amastigotes en
dc.subject In vivo en
dc.subject Hepatic en
dc.subject Histology en
dc.subject Spleen en
dc.title Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection en
dc.type Article-E en
dc.citation.issue 12 en
dc.citation.jtitle PLoS Neglected Tropical Diseases en
dc.citation.volume 6 en
dc.citation.pages e1987 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/23301108
dc.citation.jabbreviation PLoS Negl Trop Dis en


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