AV-101 · program

AV-101 (L-4-chlorokynurenine) for Levodopa-induced dyskinesia in Parkinson's disease

Phase 1SuspendedVistagen Therapeutics, Inc. (VTGN)

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, for dyskinesia in Parkinson's disease patients on levodopa therapy (LID). The FDA cleared Vistagen's IND for a Phase 2 study in LID on 2020-01-30, supported by primate data: in MPTP-lesioned monkeys AV-101 250 mg/kg twice daily reduced levodopa-induced dyskinesia by about 25% while preserving levodopa's antiparkinsonian response. The planned Phase 2 trial (NCT04147949, a randomized, double-blind, placebo-controlled crossover proof-of-concept study in about 20 patients, primary endpoint Unified Dyskinesia Rating Scale) was registered in November 2019 but never opened; its last registry update (May 2021) lists it as not yet recruiting. Vistagen first ran a Phase 1B study of AV-101 with probenecid in healthy volunteers (NCT05280054) to explore raising brain exposure. As of the 10-K filed 2026-06-15, Vistagen names LID as a potential use but does not plan further development of AV-101 on its own and is looking for a third-party partner, so the program is recorded as suspended.

Data current as of

Development timeline

Phase 1Nov 2019 – Jun 2026
  1. Vistagen's FY2026 10-K: 'We do not anticipate further development and commercialization of AV-101 on our own', while assessing a path forward with a third party for LID, neuropathic pain or other NMDAR-related disorders. The date is the filing date (an upper bound); the FY2023 10-K (2023-06-28) still said the company was 'preparing for Phase 2A development of AV-101, on our own or with collaborators'.↗
  2. FDA cleared the IND for a Phase 2 study of AV-101 in levodopa-induced dyskinesia in Parkinson's disease. The clinical stage reached is Phase 1 (healthy-volunteer safety/PK studies), as the planned Phase 2 trial NCT04147949 never started.↗
  3. IND/CTA clearanceFDA clears IND for Phase 2 study of AV-101 in levodopa-induced dyskinesia↗
  4. Trial registeredPhase 2 LID study of AV-101 (NCT04147949) registered on ClinicalTrials.gov

Clinical trials in Levodopa-induced dyskinesia in Parkinson's disease

NCT04147949VSG-CL-004Phase 2Unknownn=20

Randomized, Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Phase 2 Study to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesia

Formulations

FormulationRouteRegimenPharmacokinetics
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.
OralOther—

Mechanism of action (compound-wide)

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.

TargetActionAffinity
NMDA receptorprimaryGRIN1Antagonist—ⓘ

← Full AV-101 compound page (identity, identifiers, all indications)

Sources

  1. NCT04147949 (VSG-CL-004) — Phase 2 AV-101 in Parkinson's disease subjects with levodopa-induced dyskinesia — ClinicalTrials.gov (U.S. National Library of Medicine)
  2. NCT05280054 (AV-101 CL005) — AV-101 alone and with probenecid in healthy subjects (drug-drug interaction) — ClinicalTrials.gov (U.S. National Library of Medicine)
  3. 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
  4. VistaGen Therapeutics Receives FDA Clearance of IND for Phase 2 Clinical Study of AV-101 as a Potential Treatment of Dyskinesia in Parkinson's Disease Patients (2020-01-30; Form 8-K Exhibit 99.1) — VistaGen Therapeutics, Inc. via SEC EDGAR