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Studies about the potential allosteric influences of thioridazine on the effects of crotamine in skeletal musculature

Grant number: 18/00014-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Mirian Akemi Furuie Hayashi
Grantee:Giovanna Bello Papa
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

Crotamine have been studied for some time and different biological activities were presented, although little is known about the molecular mechanism of action involved in its myotoxic effect, which was the first to be described and is characterized by the immobilization of the skeletal muscle of rodents. We have recently demonstrated that this effect involves the action of crotamine on sodium channels, preventing their closure, and direct action as a blocker of the potassium channels demonstrated by electrophysiology. In vivo pilot studies, performed by the group, point to the possibility that the action of crotamine is not only peripheral but also with possible central effects. Concomitant injection of crotamine and antipsychotic thioridazine in mice (in vivo) allowed to observe the potentiation of both immobilization effect on the hind limbs of rodents promoted by crotamine and sedative effect of thioridazine. Thus, we suggest here that these two compounds may present a common molecular pathway, and with relevance for the eventual identification of other molecular targets of crotamine in rodents. Therefore, it is expected in this study to better understand the mechanisms that lead to the hind limb immobilization effect, without involving the functioning of the front legs by exploring the influence determined by the presence of the antipsychotic on crotamine's effects. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PORTA, LUCAS C.; CAMPEIRO, JOANA D.; PAPA, GIOVANNA B.; OLIVEIRA, EDUARDO B.; GODINHO, ROSELY O.; RODRIGUES, TIAGO; HAYASHI, MIRIAN A. F. In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine. Toxicon, v. 185, p. 64-71, OCT 15 2020. Web of Science Citations: 0.

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