Two New βN-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity

Abstract

In this work, we describe a new route for the synthesis and the antinociceptive effects of two new βN-alkanoyl-5-hydroxytryptamides (named C20:0-5HT and C22:0-5HT). 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 C20:0-5HT and C22:0-5HT 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 C20:0-5HT or C22:0-5HT. 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 βN-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.

How Does LC/MS Compare to UV in Coffee Authentication and Determination of Antioxidant Effects? Brazilian and Middle Eastern Coffee as Case Studies

“…All compounds shared the same fragment ion at m/z 160, corresponding to 5-hydroxy tryptamine, confirmed by their UV λ max at 226 nm detected in both green and roasted samples of coffee seeds, in agreement with previous reports ( Supplementary Figures S19 and S20 ) [ 44 , 45 ]. C-5HTs have been reported as present in the insoluble phase of the waxy surface of coffee seeds and as possessing antinociceptive and anti-inflammatory effects [ 51 ]. However, these compounds were reported to have an irritant effect on the stomach mucosa in high doses, manifesting in gastric discomfort.…”