Blixeprodil,https://iris.who.int/bitstream/handle/10665/380497/9789240107038-eng.pdf "blixeprodilum blixeprodil (2R)-2-(4-fluorophenyl)-2-(methylamino)cyclohexan-1-one N-methyl-D-aspartate (NMDA) receptor antagonist" also known by its developmental code name GM-1020 or as (R)-4-fluorodeschloroketamine ((R)-4-FDCK), is an NMDA receptor antagonist related to ketamine which is under development for the treatment of major depressive disorder, bipolar depression, and other depressive disorders. It is taken by mouth.
Pharmacology
Pharmacodynamics Blixeprodil is acts as an antagonist at the PCP site of NMDA receptors, with a Ki of 3.25 µM.
Pharmacokinetics The drug is orally active, in contrast to the poor oral bioavailability of ketamine. Its oral bioavailability is >60%. The time to peak levels of blixeprodil is 1.5hours and its elimination half-life is 4.3hours.
Chemistry The drug is a close analogue of ketamine, with a 4-fluoro group instead of a 2-chloro group on the phenyl ring and in (2R)-enantiopure form.
Research Blixeprodil is being developed by Gilgamesh Pharmaceuticals. As of July 2024, it was in phase 2 clinical trials for major depressive disorder and bipolar depression and is in phase 1 trials for other depressive disorders. In January 2026, Gilgamesh announced positive topline results from its Phase 2a study of blixeprodil in major depressive disorder.
Blixeprodil shows antidepressant-like effects in rodents. It appears to have a greater separation between antidepressant-like and ataxia-inducing doses than ketamine in rodents and hence might have better tolerability. Whereas ketamine shows only 3-fold separation between antidepressant-like and ataxic doses, there was 13-fold separation for blixeprodil, and it did not produce hyperlocomotion at doses >20-fold higher than the minimum antidepressant-like dose. In relation to the preceding, blixeprodil is claimed to be non-dissociative at therapeutic doses. However, dissociative and other related effects have been observed at low incidences and at higher doses.
See also List of investigational antidepressants List of investigational hallucinogens and entactogens 2-Fluorodeschloroketamine 3-Fluorodeschloroketamine Fluorexetamine
References