Drug Discovery in Neuropsychiatric Diseases: therapeutic opportunities beyond the classic aminergic system
Prof. Santiago J. Ballaz E-Mail
Full Professor of Biology & Biomedicine, School of Biological Sciences & Engineering, Yachay Tech University, Hacienda San José s/n, San Miguel de Urcuquí, Ecuador
Research Keywords: altitude sickness, COVID-19, data mining, molecular biology, neuropharmacology, parkinson disease, psychopharmacology, toxicology
Prof. Fernando Albericio E-Mail
Research Professor, School of Chemistry, Universities of KwaZulu-Natal, Durban, South Africa; Full Professor, Department of Organic Chemistry, Universidad de Barcelona, Barcelona, Spain
Innovation is essential for the pharmaceutical research and development of novel treatments for CNS disorders. Biogenic amines have been the primary target in neuropsychiatric conditions, yet their pharmacological intervention lacks definitive disease-altering therapeutic efficacy. Failures in the target identification and target validation effort, as reflected by the poor ability of current bioassays and animal models to predict efficacy may be the reasons for the low pace progress in the field of neuropsychopharmacology. In this vein, aminergic systems interact with a myriad of factors that modulate their activity. These factors include peptides of either gastrointestinal (e.g., CCK) or neural origin (e.g., opioids, pituitary and hypothalamic peptides), neurotransmitter proteins like POMC, and the FGF- and CRH-families, humoral factors such as glucocorticoids, NGF, insulin, interleukins, prostaglandins, sex and thyroid hormones, endocannabinoids and even gases (NO, CO and SH2). Aligned well with the poly-pharmacology paradigm shift in drug discovery, targets falling outside classic neurotransmitters offer great opportunities to discover repurposing drug candidates for complex psychiatric disorders. As an illustrative example, non-steroidal antiinflammatory drugs (NAIDs) are now recognized as promising strategies to treat major depression given the link between the activation of the immune system and sickness behavior. A deeper understanding of the neurobiology and pharmacology of non-conventional systems of neurotransmission like for instance those mediated by the endocannabinoid system, sex hormones, gastrointestinal neuropeptides and gases may be a better research strategy to develop novel drugs that overcome the paucity of treatments for neuropsychiatric indications.
Keywords: biogenic amines, endogenous cannabinoids, gases, gonadal steroid hormones, neuropsychiatry, neurotransmitter agents, peptide hormones, thyroid hormones