Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin.
J Physiol
; 596(10): 1833-1845, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29063617
ABSTRACT
Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from onchocerciasis and lymphatic filariasis. It was discovered by Satoshi Omura and William C. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. It kills parasites by activating glutamate-gated Cl- channels, and it also targets several ligand-gated ion channels and receptors, including Cys-loop receptors, P2X4 receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G-protein-gated inwardly rectifying K+ channel, and also identified the structural determinant for the activation. In this review, we aim to provide an update and summary of recent progress in the identification of IVM targets, as well as their modulation mechanisms, through molecular structures, chimeras and site-directed mutagenesis, and molecular docking and modelling studies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ivermectina
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Ativação do Canal Iônico
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Receptores Citoplasmáticos e Nucleares
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Canais de Cloreto
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Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G
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Receptores Purinérgicos P2X4
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Antiparasitários
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article