Amorim Jorge Luis, Lima Fernanda Alves, Brand Ana Laura Macedo, Cunha Silvio, Rezende Claudia Moraes, Fernandes Patricia Dias
Laboratório de Farmacologia da Dor e da Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Centro de Tecnologia, Laboratório de Análise de Aromas, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
Biomedicines. 2021 Apr 22;9(5):455. doi: 10.3390/biomedicines9050455.
In this work, we describe a new route for the synthesis and the antinociceptive effects of two new -alkanoyl-5-hydroxytryptamides (named C-5HT and C-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C-5HT and C-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C-5HT or C-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new -alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects.
在本研究中，我们描述了两种新型α-烷酰基-5-羟基色胺（命名为C-5HT和C-5HT）的合成新路线及其抗伤害感受作用。使用热诱导（对热板的反应，热板模型）或化学诱导（对爪注射福尔马林、辣椒素或谷氨酸后的舔舐反应）伤害感受的知名模型评估抗伤害感受活性。在给予C-5HT或C-5HT前30分钟，使用纳洛酮（阿片受体拮抗剂，1毫克/千克）、阿托品（毒蕈碱受体拮抗剂，1毫克/千克）、AM251（大麻素CB1受体拮抗剂，1毫克/千克）或昂丹司琼（5-HT3血清素能受体拮抗剂，0.5毫克/千克）评估C-5HT和C-5HT的作用机制。两种物质均通过减少福尔马林、辣椒素和谷氨酸诱导的舔舐行为并增加热板模型中的潜伏期时间而呈现出显著效果。阿片能、毒蕈碱、大麻素和血清素能途径似乎参与了抗伤害感受活性，因为它们的拮抗剂逆转了观察到的效果。由于耐受小鼠在用这两种化合物治疗时表现出较少的抗伤害感受，阿片受体部分参与其中。我们的数据显示了一种更快、更简单的新型α-烷酰基-5-羟基色胺的合成路线。两种化合物均表现出显著的抗伤害感受作用。这些新化合物可作为合成具有潜在抗伤害感受作用类似物的骨架。
