Data Supports Potential of Negative Allosteric Modulators for Anxiety and Fear-Related Disorders

Newly published data shows negative allosteric modulator targeting metabotropic glutamate receptor 7 (mGlu7) may be transformative in treating anxiety and fear-related disorders such as posttraumatic stress disorder.¹ Preclinical data from Addex suggests mGlu7 modulation with ADX71743 can alter reconsolidation of fear memories, a potential intervention point in anxiety and trauma-related disorders.

Ron Stoop, PhD, paper author and assistant professor at the Center for Psychiatric Neurosciences, noted that “this research shows that 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.”¹

The study, from the Center for Psychiatric Neurosciences in Switzerland, evaluated ADX71743, a selective mGlu7 negative allosteric modulator, in relation to models of fear learning and memory. Data showed that modulation of mGlu7 can selectively interfere with fear memory reconsolidation.² The process of restabilizing fear memories after recall is increasingly being recognized as a place for intervention in anxiety and trauma-related conditions. In the study, administration of ADX71743 in rats directly into the lateral amygdala or systemically showed disruption of fear memory reconsolidation. The effect on memory reconsolidation was specific to the conditioned stimulus, required fear memory recall, occurred in a defined time window after recall, and significantly decreased reinstatement of fear.

Analysis of electrophysiology also provided support for mGlu7 target engagement. The drug modulated glutamatergic transmission at thalamus to amygdala synapses, which are crucial for fear learning. In baseline conditions, ADX71743 increased spontaneous excitatory signaling, and under high-stimulation conditions it prevented long-term potentiation. Long term potentiation is known to be a process associated with memory formation at the cellular level. Synaptic effects similar to those in rodent models were found in human brain tissue models. Because the findings were similar in both rodent and human tissue samples, the study provides early validation for translation.

The mGlu7 receptor is one of the most expressed in the family of mGlu receptors and is thought to play an important role in central nervous system functions including emotional and stress reactivity, learning, memory, and attention. Receptor mGlu7 has been considered a promising target for potential treatment of psychiatric disorders, including posttraumatic stress disorder, obsessive compulsive disorder, anxiety, depression, substance use disorder, and schizophrenia.

“Anxiety and stress-related disorders remain among the most prevalent neuropsychiatric conditions globally, with many patients experiencing incomplete or transient responses to existing therapies. This is because drugs used to treat anxiety disorders have mainly targeted symptoms and often require continuous use, such as benzodiazepines, which can carry risks of tolerance, dependence and relapse after discontinuation,” said Tim Dyer, chief executive officer of Addex, in a press release. He emphasized that “this new research, targeting memory reconsolidation, provides a different therapeutic avenue to explore and continues to support our long-term belief that targeting mGlu7 with negative allosteric modulators is a differentiated mechanism to treat anxiety and fear-related disorders.”

References

1. Addex announces publication o preclinical data supporting potential of mGlu7 negative allosteric modulators to transform anxiety and fear-related disorder treatment. Press release. February 3, 2026. Accessed February 4, 2026. https://www.globenewswire.com/news-release/2026/02/03/3230712/0/en/Addex-Announces-Publication-of-Preclinical-Data-Supporting-Potential-of-mGlu7-Negative-Allosteric-Modulators-to-Transform-Anxiety-and-Fear-Related-Disorder-Treatment.html

2. Ciobanu AC, Caseiro DM, Niu R, et al. Negative allosteric modulation of mGlu7 disrupts fear memory reconsolidation and glutamatergic signaling in rat and human brain tissue. Mol Psychiatry. 2026;31:976–986.