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Antimicrob Agents Chemother. 2019 Sep 16. pii: AAC.01208-19. doi: 10.1128/AAC.01208-19. [Epub ahead of print]

Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.

Author information

1
Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil.
2
Instituto de Física, Universidade de São Paulo, São Paulo, SP, Brazil.
3
Laboratório de Inflamação e Imunologia, Universidade Guarulhos, Guarulhos, SP, Brazil.
4
Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
5
Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil. josuem@usp.br moraesnpdn@gmail.com.

Abstract

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.

PMID:
31527034
PMCID:
PMC6879219
[Available on 2020-05-21]
DOI:
10.1128/AAC.01208-19

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