Addex Therapeutics announced the publication of preclinical research in Molecular Psychiatry demonstrating that targeting metabotropic glutamate receptor 7 (mGlu7) with negative allosteric modulators (NAM) may offer a new approach to treating anxiety and fear-related disorders, including post-traumatic stress disorder (PTSD).
Study Design and Findings
Scientists from the Center for Psychiatric Neurosciences in Lausanne, Switzerland, evaluated the effects of ADX71743, a highly selective mGlu7 NAM, in established models of fear learning and memory. The research focused on how mGlu7 modulation can interfere with fear memory reconsolidation—the brain process that re-stabilizes fear memories after recall. When fear memories are recalled, they temporarily enter a labile state during which they can be modified, according to the findings.
In the study, administration of ADX71743 either directly into the lateral amygdala or systemically disrupted fear memory reconsolidation in rats. The effect was specific to the conditioned stimulus and significantly decreased reinstatement of fear. Electrophysiological analyses showed that ADX71743 modulated glutamatergic transmission at thalamus-to-amygdala synapses critical for fear learning. Under baseline conditions, the compound increased spontaneous excitatory signaling, while under high-stimulation conditions it prevented long-term potentiation, a cellular process associated with memory formation.
Clinical Implications
According to Tim Dyer, CEO of Addex, existing anxiety disorder treatments have mainly targeted symptoms and often require continuous use, such as benzodiazepines, which can carry risks of tolerance, dependence and relapse after discontinuation. The new research targeting memory reconsolidation provides “a different therapeutic avenue to explore,” Dyer stated.
Prof. Ron Stoop from the Center for Psychiatric Neurosciences noted that the research demonstrates “fear memories can be weakened by targeting reconsolidation with a drug acting on mGlu7. It offers a realistic path towards a time-limited pharmacological intervention, which combined with memory recall, could reduce pathological fear more durably than continuous symptom-suppressing medication.”
Notably, similar synaptic effects were observed in human brain tissue, mirroring findings in rodent models, providing early translational validation. Addex previously developed several novel chemical series of mGlu7 NAMs, which were included in the Neurosterix spin-out transaction.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://menafn.com/1110686434/Addex-Announces-Publication-Of-Preclinical-Data-Supporting-Potential-Of-Mglu7-Negative-Allosteric-Modulators-To-Transform-Anxiety-And-Fear-Related-Disorder-Treatment