title: Antischistosomal activity of a calcium channel antagonist on schistosomula and adult Schistosoma mansoni worms.
abstract: Current schistosomiasis control strategies are largely based on chemotherapeutic agents and a limited number of drugs are available today. Praziquantel (PZQ) is the only drug currently used in schistosomiasis control programs. Unfortunately, this drug shows poor efficacy in patients during the earliest infection phases. The effects of PZQ appear to operate on the voltage-operated Ca2+ channels, which are located on the external Schistosoma mansoni membrane. Because some Ca2+ channels have dihydropyridine drug class (a class that includes nifedipine) sensitivity, an in vitro analysis using a calcium channel antagonist (clinically used for cardiovascular hypertension) was performed to determine the antischistosomal effects of nifedipine on schistosomula and adult worm cultures. Nifedipine demonstrated antischistosomal activity against schistosomula and significantly reduced viability at all of the concentrations used alone or in combination with PZQ. In contrast, PZQ did not show significant efficacy when used alone. Adult worms were also affected by nifedipine after a 24 h incubation and exhibited impaired motility, several lesions on the tegument and intense contractility. These data support the idea of Ca2+ channels subunits as drug targets and favour alternative therapeutic schemes when drug resistance has been reported. In this paper, strong arguments encouraging drug research are presented, with a focus on exploring schistosomal Ca2+ channels.
authors.affiliation: Laboratório de Esquistossomose, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, Brasil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Silva-Moraes
authors.forename: Flávia Fernanda Bubula
authors.initials: FF
authors.lastname: Couto
authors.forename: Marah Mileib
authors.initials: MM
authors.lastname: Vasconcelos
authors.forename: Neusa
authors.initials: N
authors.lastname: Araújo
authors.forename: Paulo Marcos Zech
authors.initials: PM
authors.lastname: Coelho
authors.forename: Naftale
authors.initials: N
authors.lastname: Katz
authors.forename: Rafaella Fortini Queiroz
authors.initials: RF
authors.lastname: Grenfell
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D012556:Schistosomicides; D011223:Praziquantel; D009543:Nifedipine
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