AV-101 · program
AV-101 (L-4-chlorokynurenine) for Neuropathic pain
- FDA Fast Track (Neuropathic Pain; Granted September 2018)
Indications for AV-101: Levodopa-induced dyskinesia in Parkinson's disease · Phase 1 Neuropathic pain · Phase 1 Major depressive disorder · Discontinued
AV-101 (L-4-chlorokynurenine), an oral prodrug of the NMDA-receptor glycine-site antagonist 7-Cl-KYNA, as a potential non-opioid treatment for neuropathic pain. The only registered clinical study in this indication is a Phase 1b healthy-volunteer study (NCT01483846, completed September 2012, collaborators Cato Research and NIDA). It tested 360, 1080 and 1440 mg/day for 14 days for safety, pharmacokinetics and effect on capsaicin-induced hyperalgesia; the study is registered under neuropathic pain. The FDA granted Fast Track designation for neuropathic pain in September 2018. No neuropathic-pain patient trial has been registered. As of its 10-K filed 2026-06-15, Vistagen names neuropathic pain as a potential use but does not plan further development of AV-101 on its own and is looking for a third-party partner.
Development timeline
- Vistagen's FY2026 10-K: no further development of AV-101 on its own; assessing a third-party path for LID, neuropathic pain or other NMDAR-related disorders. Filing date used as an upper bound.↗
- Phase 1b multiple-dose study in healthy volunteers with a capsaicin-induced hyperalgesia model (NCT01483846) reached actual primary completion in September 2012 (day not given; month-end used).
Clinical trials in Neuropathic pain
NCT01483846VSG-CL-002Phase 1Completedn=50
A Phase 1b, Single-Site, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study: Safety, Pharmacokinetics, and Antihyperalgesic Activity of Multiple Doses of AV-101 on Capsaicin-Induced Pain in Healthy Volunteers
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| AV-101 oral capsule Oral capsules. ELEVATE (adjunctive MDD): 1440 mg daily for 14 days. NIMH TRD crossover: 1080 mg/day for 7 days then 1440 mg/day for 7 days. Phase 1b healthy volunteers: 360, 1080 or 1440 mg daily for 14 days. Planned LID Phase 2: '1440 mg ... administered twice a day orally' per the registry arm text. Drug-interaction study: single 360 mg capsule alone or 2 h after 1000 mg probenecid. | Oral | Other | — |
Mechanism of action
AV-101 (4-Cl-KYN) is an oral prodrug that targets the NMDA receptor. Its active metabolite, 7-chloro-kynurenic acid (7-Cl-KYNA), is a potent and selective full antagonist of the glycine (co-agonist) binding site of the NMDA receptor and inhibits receptor function. Unlike ketamine and many other NMDA antagonists, 7-Cl-KYNA is not an ion-channel blocker. Vistagen reports that an extensive receptor screen found no off-target binding of AV-101 or 7-Cl-KYNA. Nonclinical results also indicate that chronic 4-Cl-KYN administration induces hippocampal neurogenesis and increases endogenous kynurenic acid, itself a functional glycine-site antagonist. A key clinical limitation is brain exposure: in the NIMH depression trial, CSF 7-Cl-KYNA was mostly below detection (<1.4 ng/mL) at 1080-1440 mg/day.
| Target | Action | Affinity |
|---|---|---|
| NMDA receptorprimaryGRIN1 | Antagonist | —ⓘ |
← Full AV-101 compound page (identity, identifiers, all indications)
Sources
- NCT01483846 (VSG-CL-002) — Phase 1b multiple-dose AV-101 in healthy volunteers, capsaicin-induced hyperalgesia — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT05280054 (AV-101 CL005) — AV-101 alone and with probenecid in healthy subjects (drug-drug interaction) — ClinicalTrials.gov (U.S. National Library of Medicine)
- Vistagen Therapeutics Form 10-K for fiscal year ended 2026-03-31 (filed 2026-06-15) — AV-101 section — Vistagen Therapeutics, Inc. via SEC EDGAR