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Anxiety and depression are common mental disorders affecting millions of people worldwide. Unsatisfactory clinical outcomes with the use of the available pharmacological interventions among some patients demand newer drugs with proven efficacy, safety, and tolerability profile. In this study, the LQFM211, LQFM213, and LQFM214 were designed from the piperazine scaffold and administered orally in mice. These mice were later evaluated in the open field, elevated plus maze, and forced swimming tests to assess the exploratory, anxiolytic, and antidepressant-like activities, respectively. The mechanism of action of these new derivatives was evaluated using flumazenil (benzodiazepine antagonist) and WAY100635 ([5-HT.sub.1A] receptor antagonist). Unlike LQFM214, the LQFM211 and LQFM213 elicited anxiolytic and antidepressant-like effects. The blockade of the effect of LQFM213 by WAY100635 suggests the involvement of the serotonergic pathway. Key words: anxiety, behavioral pharmacology, depression, medicinal chemistry L'anxiete et la depression sont des maladies mentales courantes, affectant des millions de personnes a l'echelle mondiale. Les resultats cliniques insatisfaisants obtenus chez certains patients avec l'utilisation des interventions pharmacologiques disponibles font augmenter la demande pour de nouveaux medicaments dotes d'un profil d'efficacite, d'innocuite et de tolerabilite avere. Dans cette etude, nous avons produit le LQFM211, le LQFM213 et le LQFM214 a partir d'un support de piperazine et les avons administres par voie orale chez des souris. Plus tard, a l'aide des tests en espace ouvert, du labyrinthe en croix sureleve et de nage forcee, nous avons evalue chez ces souris les activites exploratrice, anxiolytique et s'apparentant a ceux des antidepresseurs, respectivement. Nous avons evalue le mode d'action de ces nouveaux derives a l'aide de flumazenil (antagoniste des benzodiazepines) et du WAY100635 (antagoniste des recepteurs 5-HT1A). Contrairement au LQFM214, le LQFM211 et le LQFM213 permettaient d'obtenir des effets anxiolytiques et d'autres effets s'apparentant a ceux des antidepresseurs. L'inhibition de l'effet du LQFM213 par le WAY100635 laisse entendre que la voie de signalisation serotoninergique participerait a ce processus. [Traduit par la Redaction] Mots-cles : anxiete, pharmacologie comportementale, depression, chimie medicinale, Introduction Anxiety and depression are the most common mental disorders and affect millions of people worldwide (Goncalves et al. 2014; Wiemann and Munhoz 2015). These diseases have great social and [...]

Background: Pharmacological treatments for mental disorders, such as anxiety and depression, present several limitations and adverse effects. Therefore, new pharmacotherapy with anxiolytic and antidepressant potential is necessary, and the study of compounds capable of interacting with more than one pharmacological target may provide new therapeutic options., Objectives: In this study, we proposed the design, synthesis of a new compound, 2-(4-((1- phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethyl acetate (LQFM192), pharmacological evaluation of its anxiolytic-like and antidepressant-like activities, as well as the possible mechanisms of action involved., Methods: Administration of LQFM192 was carried out prior to the exposure of male Swiss mice to behavioral tests, such as the elevated plus-maze and forced swimming test. The involvement of the serotonergic system was studied by pretreatment with WAY-100635 or p-chlorophenylalanine (PCPA) and the involvement of the benzodiazepine site of the GABAA receptor by pretreatment with flumazenil., Results: The treatment with LQFM192 at doses of 54 and 162 μmol/kg demonstrated anxiolyticlike activity that was blocked by WAY-100635, PCPA, and flumazenil pretreatments. The potential antidepressant-like activity was visualized at the same doses and blocked by WAY-100635 and PCPA., Conclusion: In summary, the anxiolytic-like activity of LQFM192 is mediated by the serotonergic system and the benzodiazepine site of the GABAA receptor, and the antidepressant-like activity through the serotonergic system., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Spiranthera odoratissima A. St.-Hil., 'manacá', is a medicinal species used in Brazil, especially in central region, for the treatment of several diseases such as pain and inflammation. In this study, the methanol/aqueous phase of the ethanol extract of the leaves of 'manacá' (MAP), at the doses of 50, 150 and 500 mg/kg was used to evaluate the anti-inflammatory and/or antinociceptive effects and the possible anti-inflammatory mechanism. The antinociceptive and anti-inflammatory activities of MAP were assessed using formalin test, carrageenan-induced paw oedema. The myeloperoxidase activity, capillary permeability, leukocyte migration and tumour necrosis factor alpha (TNF-α) levels were evaluated in pleural exudate. The MAP reduced the licking time only in the later phase of formalin test, and showed anti-inflammatory activity by reducing the paw oedema, migration cell, myeloperoxidase activity, capillary permeability and TNF-α levels. In conclusion, we confirmed the inflammatory activity of MAP and affirm that this effect involves the reduction of TNF-α level.