Produção Nacional
First Evaluation of the Anxiolytic-Like Effects of a Bromazepam-Palladium Complex in Mice
2022; RELX Group (Netherlands); Linguagem: Inglês
10.2139/ssrn.4119250
ISSN1556-5068
AutoresMirella P.S. Vieira, Ozileudiane B. S. Silva, Gabriela F. Souza, Gabriela T. S. Cavalcante, Fernanda Maria Araújo de Souza, José Renato de Oliveira e Silva Neto, Dannyele Cynthia Santos Pimentel Nicácio, Allysson H. Q. Silva, Artur V. Silva, Axel Helmut Rulf Cofré, Mariana A. Amorós, Walleska B. Z. G. B. Correia, Daniel Leite Góes Gitaí, Olagide Wagner de Castro, J. Junkes, Filipe Silveira Duarte, Jéssica S. Guedes, Fábio César Sousa Nogueira, Mário R. Meneghetti, Marcelo Duzzioni,
Tópico(s)Pharmacological Receptor Mechanisms and Effects
ResumoA significant fraction of patients is affected by persistent fear and anxiety. There are currently several anxiolytic drug options, although the clinical outcome of these existing drugs is not able to completely control symptoms. Here, we evaluated the effects of a bromazepam-palladium derivative [2-{(7-bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-il)pyridinyl-κ2-N,N}chloropalladium(II)], [(BMZ)PdCl2 ], on fear, anxiety and memory-related behaviors in mice. For this, female Swiss mice were treated intraperitoneally (i.p.) with saline (NaCl 0.9%) or [(BMZ)PdCl2] (0.5, 5.0, or 50 μg/kg). After 30 minutes, different anxiety (elevated plus maze and light-dark box), locomotion (open field) and memory (step-down passive avoidance) tests were performed. We also evaluated the acute toxicity of [(BMZ)PdCl2] using a cell viability assay (neutral red uptake assay), and whether its mechanism of action involves the GABAA receptor complex by pre-treating animals with flumazenil (1.0 mg/kg, i.p., an antagonist of GABAA receptor-benzodiazepine complex). Our results demonstrated that [(BMZ)PdCl2] induces an anxiolytic-like phenotype in the elevated plus-maze test and that this effect was blocked by flumazenil. [(BMZ)PdCl2] did not promote any significant change in the light-dark box, open field, and step-down passive avoidance tests. In the acute toxicity assay, [(BMZ)PdCl2] presented IC50 and LD50 values of 217.85±59.75 µg/mL and 779.59±80.41 mg/kg, respectively, and GSH category 4. Taken together our results showed that the anxiolytic-like effect of acute treatment with [(BMZ)PdCl2] occurs through modulation of the benzodiazepine site in the GABAA receptor complex. There are also indications that [(BMZ)PdCl2] does not promote sedation and amnesia and presents the same toxicity as the bromazepam prototype.
Referência(s)