Blixeprodil
Pharmaceutical compound
From Wikipedia, the free encyclopedia
Blixeprodil,[5] 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.[1][6][2][3][7][8] It is taken by mouth.[1][2][3]
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| Clinical data | |
|---|---|
| Other names | GM-1020; GM1020; (R)-4-Fluorodeschloroketamine; (R)-4-FDCK; (R)-4FDCK |
| Routes of administration | Oral[1][2][3] |
| Drug class | NMDA receptor antagonist[1][2][3] |
| Pharmacokinetic data | |
| Bioavailability | >60%[4] |
| Elimination half-life | 4.3 hours[4] |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| Chemical and physical data | |
| Formula | C13H16FNO |
| Molar mass | 221.275 g·molâ1 |
| 3D model (JSmol) | |
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The drug is orally active, in contrast to the poor oral bioavailability of ketamine.[3] Its oral bioavailability is >60%.[4][9] The time to peak levels of blixeprodil is 1.5 hours and its elimination half-life is 4.3 hours.[4] In a clinical study comparing it with the serotonergic psychedelic bretisilocin (GM-2505), both blixeprodil and bretisilocin produced hallucinogenic effects.[10]
Blixeprodil shows antidepressant-like effects in rodents.[3][11][4][9] It appears to have a greater separation between antidepressant-like and ataxia-inducing doses than ketamine in rodents and hence might have better tolerability.[3][7][9] 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.[9] In relation to the preceding, blixeprodil is claimed to be non-dissociative at therapeutic doses.[2][4] However, dissociative and other related effects have been observed at low incidences and at higher doses.[4]
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.[12] 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.[13]
Blixeprodil is being developed by Gilgamesh Pharmaceuticals.[1][6][2] 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.[1][6][2]