A newly published study shows that ADX71743, a selective mGlu7 inhibitor, significantly modulates sleep-wake regulation and stress-related neurochemistry in animal models.
Key takeaways:
- Preclinical data shows ADX71743 increased wakefulness by up to 100% while reducing both REM and non-REM sleep in rats.
- The compound delayed NREM and REM sleep onset by nearly two-fold for two hours after dosing, without altering motor activity.
- Findings validate mGlu7 as a promising therapeutic target for central nervous system disorders, including anxiety and PTSD.
Addex Therapeutics recently shared the publication of new preclinical research demonstrating that ADX71743, a selective negative allosteric modulator of metabotropic glutamate receptor 7 (mGlu7), significantly modulates sleep-wake regulation and stress-related neurochemistry.
The data, published in the International Journal of Neuropsychopharmacology, expands the growing body of evidence supporting mGlu7 as an important mechanism regulating key brain functions and a therapeutic target across a range of central nervous system disorders, including mood disorders, anxiety disorders, post-traumatic stress disorder (PTSD), and other conditions associated with dysregulated stress responses.
“This publication demonstrating the role of mGlu7 modulation in sleep and wakefulness adds another important piece of evidence supporting the therapeutic potential of targeting these receptors with allosteric modulation,” says Tim Dyer, CEO at Addex, in a release. “ADX71743 has consistently helped establish the biological role of mGlu7 across multiple disease-relevant models, and we are pleased to see this body of work continue to strengthen the scientific rationale for Neurosterix’s ongoing development of this exciting target.”
In the study, ADX71743 increased wakefulness by up to 100% while reducing rapid eye-movement (REM) sleep by up to 100% and non-REM (NREM) sleep by up to 75% in rats. The compound also delayed NREM and REM sleep onset by nearly two-fold for two hours after dosing, without altering motor activity or body temperature.
The compound altered stress-induced changes in key neurotransmitters, including glutamate, GABA, and monoamines, across multiple brain regions in awake animals. Specifically, ADX71743 attenuated stress-related changes in GABA and serotonin, maintaining higher levels in the ventral hippocampus than in vehicle-treated controls. These neurochemical effects are consistent with the modulation of stress-responsive neural circuits.
Together, these findings further validate the pharmacological profile of selective mGlu7 inhibition in vivo and provide additional support for the therapeutic potential of this novel mechanism. ADX71743 was discovered by Addex and now forms part of the mGlu7 program being advanced by Neurosterix.
