Synthesis of Novel Pyrido[1,2-c]pyrimidine Derivatives with 6-Fluoro-3-(4-piperidynyl)-1,2-benzisoxazole Moiety as Potential SSRI and 5-HT1A Receptor Ligands

Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidine (6a–i) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine (7a–i) derivatives were synthesized. The chemical structures of the new compounds were confirmed by 1H and 13C NMR spectroscopy and ESI-HRMS spectrometry. The affinities of all compounds for the 5-HT1A receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays. The test compounds demonstrated very high binding affinities for the 5-HT1A receptor of all derivatives in the series (6a–i and 7a–i) and generally low binding affinities for the SERT protein, with the exception of compounds 6a and 7g. Extended affinity tests for the receptors D2, 5-HT2A, 5-HT6 and 5-HT7 were conducted with regard to selected compounds (6a, 7g, 6d and 7i). All four compounds demonstrated very high affinities for the D2 and 5-HT2A receptors. Compounds 6a and 7g also had high affinities for 5-HT7, while 6d and 7i held moderate affinities for this receptor. Compounds 6a and 7g were also tested in vivo to identify their functional activity profiles with regard to the 5-HT1A receptor, with 6a demonstrating the activity profile of a presynaptic agonist. Metabolic stability tests were also conducted for 6a and 6d.

Plantas medicinales como alternativa terapéutica para el trastorno Depresivo Mayor (DMD)

Objective: To review the antidepressant activity and mechanisms of action of plants that have antidepressant action. Literature Review: The use of plants for medicinal purposes has been used as an adjunct to the treatment of depression due to easy access by the population, few side effects and lower cost. Based on the studies, the plants St. John's wort, ground turmeric, anona and lavender have antidepressant potential for acting in different ways in depression, either by inhibiting the reuptake of serotonin or by modulation in the dopaminergic and serotonergic pathways. Final Considerations: From the studies of the mechanisms of action it was found that the plants studied can modulate the brain signaling pathways responsible for the patient's mood, with the reuptake of serotonin (inhibition of the serotonin transporter protein) the main mechanism of action shared between them. In addition, some of these plants can modulate not only the concentrations of serotonin in the synaptic cleft, but also dopamine. It is worth mentioning that, although these actions have been scientifically proven, much research is still needed to ensure the safe use of these agents as herbal medicines in the alternative or adjunctive treatment of depressive disorders.