Anxiety disorders are the most common form of mental disorder, affecting more than 300 million people around the world. Aside from psychological interventions, anxiety disorders are commonly treated using antidepressant drugs such as serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Although the therapeutic effect of these drugs has improved over time with new generations, both SSRIs and SNRIs suffer from issues related to safety and tolerability as well as slow onset of action.
In a recent study, published in the scientific journal Neuropharmacology, Australian researchers at Bionomics Ltd present a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) with anxiolytic and antidepressant effect in rodents. Moreover, the presented results show that the demonstrated therapeutic effect is possible to obtain without the many side effects associated with currently used therapies, creating a potential new way to treat anxiety and stress-related disorders.
In their work, the researchers used Dynaflow Resolve in electrophysiological assays to determine the effect of the α7 nAChR modulatorin vitro. Dose-response analysis performed both with and without presence of receptor agonists showed that the studied compound functions as a negative allosteric modulator and that it doesn't have the ability to induce α7 nAChR currents by itself. Additionally, experiments made using related receptor proteins showed that the antagonistic effect is selective for α7 nAChR, minimizing the risk for unwanted side effects.
These characteristics are things that make allosteric modulators particularly interesting as drug compounds. As O’Connor et al write in the article: “Allosteric modulators possess several advantages asprospective therapeutics, including a greater chance of being subunit selectivedue to binding at less conserved sites. Allosteric effects can only be achieved in the presence of endogenous agonists, thus spatiotemporal signaling of natural ligands is maintained.”
The authors also state the finding that the most efficacious compound found in their initial screening was an allosteric inhibitor of α7nAChR as particularly noteworthy. Because of their positioning in neuros affected by GABA and glutamate in regions such as hippocampus, amygdala, and pre-frontal cortex(PFC), α7 nAChRs have an interesting role to play in the regulation of neuronal excitability. This, together with the presented results point to a broaderpotential for future new treatment opportunities.
We are very happy that the researchers at Binomics have chosen to use Dynaflow Resolve in their work. We are excited to follow their continued development efforts and to see what the broader potential that their research indicates might bring.
Read the article in Neuropharmacology