New research suggests that targeting the metabotropic glutamate receptor 7 (mGlu7) with a specific type of drug may offer a novel approach to treating anxiety and fear-related disorders, including posttraumatic stress disorder (PTSD). The findings, published recently, demonstrate that modulating mGlu7 can interfere with the process by which the brain reconsolidates fear memories – essentially, the way memories are restabilized when recalled.
The study, conducted by scientists at the Center for Psychiatric Neurosciences (CNP, CHUV/UNIL) in Lausanne, Switzerland, investigated the effects of ADX71743, a highly selective mGlu7 negative allosteric modulator (NAM). Researchers found that this modulator could disrupt fear memory reconsolidation in animal models. This disruption occurred when fear memories were recalled and within a specific timeframe following recall, leading to a reduction in fear responses.
“This research shows that fear memories can be weakened by targeting reconsolidation with a drug acting on mGlu7,” explained Ron Stoop, PhD, a paper author and assistant professor at the Center for Psychiatric Neurosciences. “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.”
The mGlu7 receptor is highly expressed in the central nervous system and plays a role in several brain functions, including emotional and stress reactivity, learning, memory, and attention. Because of this multifaceted role, it has emerged as a promising target for a range of disorders beyond anxiety and PTSD, such as obsessive-compulsive disorder (OCD), depression, drug abuse, and schizophrenia.
The mechanism behind ADX71743’s effect involves modulating glutamatergic transmission between the thalamus and the amygdala – brain regions critical for fear learning. Electrophysiological studies showed that the drug increased spontaneous excitatory signaling and prevented long-term potentiation (LTP), a process associated with memory formation, under high stimulation conditions. Importantly, similar synaptic effects were observed in human brain tissue models, providing early translational validation for targeting reconsolidation pathways in anxiety and trauma-related disorders.
Currently, many treatments for anxiety and stress-related disorders focus on managing symptoms and often require continuous use. These treatments, such as benzodiazepines, can carry risks of tolerance, dependence, and relapse upon discontinuation. The potential of mGlu7 NAMs lies in their ability to act as time-limited interventions, paired with memory recall, potentially offering a more targeted and durable reduction in pathological fear.
According to Tim Dyer, CEO of Addex Therapeutics, the company developing ADX71743, “Anxiety and stress-related disorders remain among the most prevalent neuropsychiatric conditions globally, with many patients experiencing incomplete or transient responses to existing therapies.” He emphasized that this new research, focusing on memory reconsolidation, represents a different therapeutic avenue to explore and reinforces the company’s belief in the potential of targeting mGlu7 with negative allosteric modulators for treating anxiety and fear-related disorders.
The study demonstrated that ADX71743’s effects on fear memory reconsolidation were specific to the conditioned stimulus, meaning it targeted the specific memory associated with the fear, and could be achieved through both direct administration into the lateral amygdala and systemic dosing, suggesting feasibility for non-invasive administration.
Addex Therapeutics announced the publication of these preclinical data on , in the journal Molecular Psychiatry. Further research will be needed to determine the safety and efficacy of mGlu7 NAMs in human clinical trials.
