Efeito antinociceptivo da benzamida N-3- (fenilselenil)prop-2-in-1-ílica em camundongos: envolvimento do sistema serotoninérgico

Abstract

Pain is a medical condition present in several pathologies as a secondary and disabling effect, in addition to being categorized as a multidimensional and multifactorial phenomenon, which involves different neurotransmitter systems, including the serotonergic. For this reason, it is necessary to obtain analgesic compounds that have greater efficacy and fewer adverse effects. Taking into account the pharmacological properties demonstrated by selenium and the benzamide nucleus, both components were incorporated into a new molecule: N-3-(phenylselenyl)prop-2-yn-1-ylic benzamide (SePB). Therefore, the present work aimed to evaluate the antinociceptive effect of this compound in mouse pain models and its interaction with serotonergic receptors. Adult male Swiss mice weighing between 25 and 30 g were used, from the Central Animal House of the Federal University of Pelotas. Initially, a time-response curve was performed in the tail immersion test and later a dose-response curve in the tail immersion, hot plate and glutamate tests. In all tests performed, the time for the animal's nociception response was evaluated. For the time-response curve, the animals received 10 mg/kg of SePB, diluted in canola oil, intragastrically, 15 minutes, 30 minutes, 1 hour or 2 hours before the tail immersion test. In the dose-response curves, doses of 1 mg/kg, 10 mg/kg and 50 mg/kg of the compound diluted in canola oil were used, administered to the animals intragastrically 30 min before the nociceptive tests. In the time-response curve, SePB increased the latency for the nociceptive response in the tail immersion test from 30 minutes, which was chosen for further tests. In the dose-response curve, performed in the tail immersion test, SePB increased the latency to the nociceptive response at all doses tested. In the hot plate and paw glutamate tests, SePB increased the latency to nociception from the dose of 10 mg/kg. These results demonstrate that SePB had an antinociceptive effect. To evaluate the serotonergic system, selective 5-HT receptor antagonists were administered, namely WAY100635 (0.5 mg/kg, subcutaneously, a 5-HT1A receptor antagonist), ketanserin (0.3 mg/kg, intraperitoneally). , a 5-HT2A/2C receptor antagonist) or ondansetron (0.5 mg/kg, intraperitoneally, a 5-HT3receptor antagonist), 15 minutes before administration of SePB (10 mg/kg, intragastric). The behavioral test was performed 30 minutes after compound administration. WAY100635 and ketanserin acted blocking the nociceptive effect presented by the compound, while ondasetron had no interaction with the effect caused by SePB. Before any experiment, the open field test was performed to assess the existence of a possible locomotor deficit, which was not identified. We conclude that SePB has an antinociceptive effect, which can be modulated by the serotonergic system, specifically through 5-HT1A and 5-HT2A/2C receptors, thus proving to be a promising compound for the treatment of pain.