Serotonin (5-HT) receptors are found throughout central and peripheral nervous systems, mainly in brain regions involved in the neurobiology of anxiety and depression. 5-HT receptors are currently promising targets for discovering new drugs for treating disorders ranging from migraine to neuropsychiatric upsets, such as anxiety and depression. It is well described in the current literature that the brain expresses seven types of 5-HT receptors comprising eighteen distinct subtypes. In this article, we comprehensively reviewed 5-HT1-7 receptors. Of the eighteen 5-HT receptors known today, thirteen are G protein-coupled receptors (GPCRs) and represent targets for approximately 40% of drugs used in humans. Signaling pathways related to these receptors play a crucial role in neurodevelopment and can be modulated to develop effective therapies to treat anxiety and depression. This review presents the experimental evidence of the modulation of the “serotonergic receptosome” in the treatment of anxiety and depression, as well as demonstrating state-of-the-art research related to phytochemicals and these disorders. In addition, detailed aspects of the pharmacological mechanism of action of all currently known 5-HT receptor families were reviewed. From this review, it will be possible to direct the rational design of drugs towards new therapies that involve signaling via 5-HT receptors.
BackgroundIt is known that local tissue injuries incurred by snakebites are quickly instilled causing extensive, irreversible, tissue destruction that may include loss of limb function or even amputation. Such injuries are not completely neutralized by the available antivenins, which in general are focused on halting systemic effects. Therefore it is prudent to investigate the potential antiophidic effects of natural and synthetic compounds, perhaps combining them with serum therapy, to potentially attenuate or eliminate the adverse local and systemic effects of snake venom. This study assessed a group of quinones that are widely distributed in nature and constitute an important class of natural products that exhibit a range of biological activities. Of these quinones, lapachol is one of the most important compounds, having been first isolated in 1882 from the bark of Tabebuia avellanedae.Methodology/Principal findingsIt was investigated the ability of lapachol and some new potential active analogues based on the 2-hydroxi-naphthoquinone scaffold to antagonize important activities of Bothrops venoms (Bothrops atrox and Bothrops jararaca) under different experimental protocols in vitro and in vivo. The bioassays used to test the compounds were: procoagulant, phospholipase A2, collagenase and proteolytic activities in vitro, venom-induced hemorrhage, edematogenic, and myotoxic effects in mice. Proteolytic and collagenase activities of Bothrops atrox venom were shown to be inhibited by lapachol and its analogues 3a, 3b, 3c, 3e. The inhibition of these enzymatic activities might help to explain the effects of the analogue 3a in vivo, which decreased skin hemorrhage induced by Bothrops venom. Lapachol and the synthetic analogues 3a and 3b did not inhibit the myotoxic activity induced by Bothrops atrox venom. The negative protective effect of these compounds against the myotoxicity can be partially explained by their lack of ability to effectively inhibit phospholipase A2 venom activity. Bothrops atrox venom also induced edema, which was significantly reduced by the analogue 3a.ConclusionsThis research using a natural quinone and some related synthetic quinone compounds has shown that they exhibit antivenom activity; especially the compound 3a. The data from 3a showed a decrease in inflammatory venom effects, presumably those that are metalloproteinase-derived. Its ability to counteract such snake venom activities contributes to the search for improving the management of venomous snakebites.
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