Abstract

Anxiety is currently a research field of great interest in neuropsychopharmacology due to the challenge for drug discovery that demands the identification of appropriate molecular targets in the case of patients with mood disorders or with comorbid conditions. 126 M. Saldías, G. Valenzuela-Barra, M. Peña-Cerda et al. Four neurotransmitter systems beyond the GABA-benzodiazepine relationship, stand out as the main focus in the study of new anxiolytic drugs. Among them, selective serotonin reuptake inhibitors (SSRIs) have received much attention and have been the focus of most intensively preclinical studies. Neuropeptides, in particular corticotropin releasing factor, such as cholecystokinin and tachykinins have also been intensively studied. In addition, it is mentioned an increase in preclinical research on the anxiety related to properties in glutamate and endocannabinoid systems. In this regard, natural products have been widely used in the treatment of anxiety disorders and as a source of bioactive heterocyclic compounds. Chrysin, a hydroxyflavone isolated from the flowers of Passiflora spp., showed to be a ligand of benzodiazepine receptors of central and peripheral nervous system. On the other hand, Apigenin, another hydroxyflavone obtained from Chamomille, displayed an anxiolytic effect in elevated plus maze assays. Moreover, Kavalactones obtained from Kava Kava, have shown significant anxiolytic effect on in vivo and in vitro assays. Cannabidiol, a terpenphenolic compound, is a constituent non-psychotomimetic of Cannabis sativa with a wide psychiatric potential, including uses as antidepressant and anxiolytic. Besides their anxiolytic effects, these compounds have been used as precursors in semisynthesis and as synthetic pattern of new drugs, with potential activity on pathophysiological targets. In the last years, the structural richness in pharmaceutical products has improved, mainly due to the adoption of metal catalyzed couplings by using Suzuki and Buchwald-Hartwig reactions. The development of catalytic synthesis of natural and synthetic compounds with pharmacological effects, allows to modulate specific properties such as electronic distribution, to study the chemical framework, which could correlate aspects such as lipophilicity or polarity, and can determine molecular reactivity, metabolic stability, therapeutic effects and toxicity. In this chapter we will review some trends in treatment of anxiety with natural compounds and transition metal-catalyzed couplings for the synthesis of new drugs with anxiolytic properties.