New Mathematical Model May Be Critical in Designing Effective Treatments for Brain Disorders

G-protein coupled receptors are present in many neurological and psychological disorders through the activation of G proteins. In addition to activating G protein, they are also able to activate proteins responsible for Other signaling pathways, thus achieving more effect at a time. These effects can be beneficial or harmful. For this reason, controlling them by directing the signal in the appropriate direction is a therapeutic goal. An example of this type of treatment is chronic pain and opioid medication treatment. Morphine exerts its therapeutic effects by binding to the μ-opioid receptor and by activating the G protein signaling pathway, but by the same receptor it also produces undesirable effects via the β-arrestin pathway. Researchers are trying to design drugs that bind to the μ-opioid receptor to specifically activate the G protein pathway.

Innovation in the design of new drugs must go hand in hand with the development of new theoretical frameworks to define reliable measures for pharmaceutical properties that need to be improved. In this study, researchers further investigated the quantification of biological signal bias by the inclusion of unbound receptor activity (constitutive activity or basal receptor activity). Thus, there is an increase in the pharmacological space available for the discovery and quantification of new agonist drugs, neutral antagonists and inverse antagonists (ligands that increase, modify or decrease the basal receptor activities).

"Given the fact that, for a specific receptor, one signaling pathway might be related to the therapeutic effects, while another could have adverse effects, the quantification of a skewed signaling pathway of the receptors is fundamental to designing more precise and less complex drugs, side effects, "said Dr. Jesús Giraldo, study coordinator and head of the Laboratory of Molecular Neuropharmacology and Bioinformatics at the Institute of Neuroscience at UAB (INc) . Dr. Giraldo said: "The next step will be to integrate the model into the systematic and systematic badysis of new drugs to verify its degree of validity in real-life situations."

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Autonomous University of Barcelona