Addex Therapeutics has published new research showing that targeting mGlu7 receptors with negative allosteric modulators can prevent fear memory reconsolidation, potentially offering a new approach to treating anxiety and PTSD.
Addex Therapeuticsa clinical-stage biopharmaceutical company developing novel small molecule allosteric modulators. neurological disorderhas published new research that could lead to new treatments for anxiety and fear-related conditions such as post-traumatic stress disorder (PTSD). Their recently published data indicate that targeting metabotropic glutamate receptor 7 (mGlu7) with negative allosteric modulators (NAMs) may provide a powerful therapeutic approach.
Aiming to reconsolidate fear memories
the studyconducted by scientists. Center for Psychiatry and Neuroscience (CNP, CHUV/UNIL) from Lausanne, Switzerland, investigated the effects of ADX71743, a highly selective mGlu7 NAM, in established animal models of fear learning and memory. The researchers found that modulating mGlu7 can selectively prevent fear memory reconsolidation, the process by which the brain restabilizes a fear memory after it has been recalled.
Anxiety and stress-related disorders remain the most prevalent neuropsychiatric disorders worldwide, and many patients experience incomplete or transient responses to existing treatments.
“Anxiety and stress-related disorders remain among the most prevalent neuropsychiatric disorders worldwide, with many patients experiencing incomplete or transient responses to existing treatments,” said Tim Dyer, CEO of Addex. “This is because drugs used to treat anxiety disorders primarily target symptoms and often require continued use, such as benzodiazepines, which carry risks of tolerance, dependence, and relapse after discontinuation. This new study targeting memory reconsolidation “It provides another therapeutic avenue to explore and continues to support our long-standing belief that targeting mGlu7 with negative allosteric modulators is a differentiated mechanism for treating anxiety and fear-related disorders.”
destroy fear memories in the brain
Fear memories are encoded in the lateral amygdala, a central hub for emotional processing. When these memories are recalled, they become temporarily unstable and can be changed. This study showed that ADX71743, administered directly to the lateral amygdala or systemically, inhibited fear memory reconsolidation in rats. This effect was specific to the conditioned stimulus, required memory recall, occurred within a defined time frame after recall, and significantly reduced fear resurgence.
Mechanistic insights from electrophysiology
Electrophysiological analysis further supported the involvement of mGlu7. ADX71743 was shown to modulate glutamatergic transmission at the thalamus-to-amygdala synapse, which is important for fear learning. Under baseline conditions, this compound increased spontaneous excitatory signaling, but under conditions of high stimulation it interfered with long-term potentiation, a key cellular process in memory formation. Similar synaptic effects were observed in human brain tissue, providing early translational validation and addressing common risk factors in central nervous system drug development.
ADX71743 was shown to modulate glutamatergic transmission at the thalamus-to-amygdala synapse, which is important for fear learning.
“This study shows that fear memories can be weakened by targeting reconsolidation with drugs that act on mGlu7. This provides a realistic route towards time-limited pharmacological interventions, which, when combined with memory retrieval, may reduce pathological fear more permanently than continuous symptom-suppressing drugs,” said study author Professor Ron Stoops, from the Center for Psychiatry and Neuroscience.
A strong foundation for drug discovery
To date, Addex has built one of the industry’s largest libraries of allosteric modulators targeting metabotropic glutamate receptors. From this library, several new chemical series of mGlu7 NAMs were identified, optimized, and formed part of the Neurosterix spinout transaction. These findings will be key in the future development of differentiated treatments for patients with anxiety and PTSD.