Vistagen Wins US Patent for Investigational NMDA Receptor Antagonist to Treat Neuropathic Pain

The US Patent and Trademark Office has granted Vistagen a patent for AV-101, an investigational non-opioid oral prodrug for the treatment of neuropathic pain. The patent extends through at least 2034 and is part of Vistagen’s broader intellectual property portfolio covering manufacturing methods and therapeutic applications of AV-101, which modulates NMDA receptor activity.

Preclinical studies published in The Journal of Pain demonstrated AV-101’s antinociceptive effects comparable to gabapentin, with an improved safety profile in hyperalgesia and allodynia models. Additional preclinical data from the Chung ligation model of pain showed AV-101’s efficacy similar to pregabalin in neuropathic pain states. Clinical data from Phase 1 trials, published in the Scandinavian Journal of Pain, indicated AV-101 was well tolerated with no significant difference in adverse events compared to placebo. While these studies were not powered to detect statistical significance in pain reduction, consistent decreases in allodynia and hyperalgesia were observed.

AV-101 (4-Cl-KYN) is a prodrug that produces 7-Cl-KYNA, an NMDA receptor modulator distinct from classic channel-blocking antagonists like ketamine. Unlike ketamine and amantadine, which act as ion channel blockers, 7-Cl-KYNA modulates NMDA receptor function without causing the adverse psychological side effects associated with traditional NMDA receptor antagonists. AV-101 has demonstrated high oral bioavailability, efficient blood-brain barrier penetration, and preferential conversion to 7-Cl-KYNA in brain regions implicated in Parkinson’s disease and neuropathic pain.

An extensive receptor screening study found no off-target binding for AV-101 or its active metabolite, suggesting a potentially favorable safety profile. Phase 1 clinical trials have indicated that AV-101 is well tolerated, with no serious adverse psychological effects or safety concerns. Compared to existing non-opioid treatments such as gabapentin and pregabalin, which are associated with sedation in some patients, AV-101 may offer a safer alternative with an improved tolerability profile.

The FDA has granted Fast Track designation to AV-101 for neuropathic pain and as an adjunctive treatment for major depressive disorder. Vistagen is actively seeking strategic partnerships to advance the clinical development and commercialization of AV-101 for neuropathic pain and other neurological disorders.