Blixeprodil
| Clinical data | |
|---|---|
| Other names | GM-1020; GM1020; (R)-4-Fluorodeschloroketamine; (R)-4-FDCK; (R)-4FDCK |
| Routes of administration | Oral |
| Drug class | NMDA receptor antagonist |
| Pharmacokinetic data | |
| Bioavailability | >60% |
| Elimination half-life | 4.3 hours |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| Chemical and physical data | |
| Formula | C13H16FNO |
| Molar mass | 221.275 g·mol−1 |
| 3D model (JSmol) | |
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Blixeprodil, 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.
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 1.5 hours and its elimination half-life is 4.3 hours.
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.
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. Hence, blixeprodil is related to arketamine ((R)-ketamine); it is said to "bet" on the notion that arketamine is importantly involved in the antidepressant effects of ketamine, in spite of arketamine having less propensity for inducing dissociation.
Blixeprodil is being developed by Gilgamesh Pharmaceuticals. As of July 2024, it is in phase 2 clinical trials for major depressive disorder and bipolar depression and is in phase 1 trials for other depressive disorders.