Role of noradrenergic and dopaminergic systems in the antinociceptive effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide in mice.

Autor: Ledebuhr KNB; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical, and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS 96010-900, Brazil., Nunes GD; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical, and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS 96010-900, Brazil., Presa MH; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical, and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS 96010-900, Brazil., Hartmann CM; Núcleo de Síntese, Aplicação e Análise de Compostos Orgânicos e Inorgânicos (NUSAACOI), Federal University of Fronteira Sul (UFFS), Cerro Largo, RS, Brazil., Godoi B; Núcleo de Síntese, Aplicação e Análise de Compostos Orgânicos e Inorgânicos (NUSAACOI), Federal University of Fronteira Sul (UFFS), Cerro Largo, RS, Brazil., Bortolatto CF; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical, and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS 96010-900, Brazil. Electronic address: cristiani.bortolatto@ufpel.edu.br., Brüning CA; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical, and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS 96010-900, Brazil. Electronic address: cesar.bruning@ufpel.edu.br.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Mar; Vol. 484, pp. 116881. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1016/j.taap.2024.116881
Abstrakt: Pain has a negative impact on public health, reducing quality of life. Unfortunately, current treatments are not fully effective and have adverse effects. Therefore, there is a need to develop new analgesic compounds. Due to promising results regarding the antinociceptive effect of N-(3-(phenylselanyl)prop-2-in-1-yl)benzamide (SePB), this study aimed to evaluate the participation of the dopaminergic and noradrenergic systems in this effect in mice, as well as its toxicity. To this, the antagonists sulpiride (D 2 /D 3 receptor antagonist, 5 mg/kg), SCH-23390 (D 1 receptor antagonist, 0.05 mg/kg), prazosin (α 1 adrenergic receptor antagonist, 0.15 mg/kg), yohimbine (α 2 -adrenergic receptors, 0.15 mg/kg) and propranolol (non-selective β-adrenergic antagonist, 10 mg/kg) were administered intraperitoneally to mice 15 min before SePB (10 mg/kg, intragastrically), except for propranolol (20 min). After 26 min of SePB administration, the open field test was performed for 4 min to assess locomotor activity, followed by the tail immersion test to measure the nociceptive response. For the toxicity test, animals received a high dose of 300 mg/kg of SePB. SePB showed an increase in the latency for nociceptive response in the tail immersion test, and this effect was prevented by SCH-23390, yohimbine and propranolol, indicating the involvement of D 1 , α 2 and β-adrenergic receptors in the antinociceptive mechanism of the SePB effect. No changes were observed in the open field test, and the toxicity assessment suggested that SePB has low potential to induce toxicity. These findings contribute to understanding SePB's mechanism of action, with a focus on the development of new alternatives for pain treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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