title: Leishmania donovani: effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Indian clinical isolates to sodium stibogluconate.
abstract: Although pentavalent antimonials are the first-line drug for treatment of visceral leishmaniasis all over the world, yet, in India, increasing number of patients are being reported to be unresponsive to sodium stibogluconate. Verapamil, a calcium channel blocker, affects drug uptake by preventing its efflux and thereby accumulation within the cell. In the present study, effect of verapamil on in vitro susceptibility of both promastigote and amastigote stages of 15 clinical isolates and standard strain of Leishmania donovani to sodium stibogluconate was evaluated by detection of acid phosphatase. Amastigotes were found more susceptible to sodium stibogluconate than the promastigotes (p<0.05) and in the presence of verapamil, IC(50) value of sodium stibogluconate was reduced only for those isolates, which had a higher IC(50). Verapamil alone did not have any effect on the parasites. The results indicate that amastigotes are more susceptible to sodium stibogluconate than promastigotes and verapamil can reverse the in vitro drug resistance of L. donovani clinical isolates to sodium stibogluconate.
authors.affiliation: Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. suresh_pallikkuth@yahoo.com
authors.forename: Ranjini
authors.initials: R
authors.lastname: Valiathan
authors.forename: M L
authors.initials: ML
authors.lastname: Dubey
authors.forename: R C
authors.initials: RC
authors.lastname: Mahajan
authors.forename: Nancy
authors.initials: N
authors.lastname: Malla
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000378:metabolism / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D002121:Calcium Channel Blockers; D014700:Verapamil; D000967:Antimony Sodium Gluconate