MIJ821
nmda modulator · rapid and sustained antidepressant signal in phase ii trial class / nmda modulatorspec sheet6 rows
MIJ821 (onfasprodil) is Novartis's entry into the decades-long line of GluN2B (NR2B)-selective NMDA drugs that runs back through eliprodil and traxoprodil to rislenemdaz, an intravenous negative allosteric modulator built for rapid-onset relief in treatment-resistant depression. It's the newest compound in this family to reach controlled human trials, and its 2025 Phase II proof-of-concept study, led by Richard Shelton and colleagues, reported rapid and sustained efficacy signals in treatment-resistant patients, a genuinely encouraging result given how many earlier NR2B-selective compounds stalled at exactly this stage. Whether MIJ821 becomes the one that finally breaks the pattern, or joins traxoprodil and rislenemdaz as another promising NR2B drug that couldn't clear Phase III, is still an open question as of this writing.
- rapid and sustained antidepressant signal reported in Phase II
- selective NR2B mechanism intended to limit broad NMDA side effects
- modern trial design building on decades of NR2B research
- MIJ821 is dosed intravenously, similar to ketamine and rapastinel, rather than orally.
- Its 2025 Phase II results make it the most recent chapter in a nearly 40-year search for a clinically successful NR2B-selective NMDA antidepressant.
Mechanism
Intravenously-dosed negative modulator selective for GluN2B (NR2B)-containing receptors, the same subunit-selective strategy pioneered by eliprodil and traxoprodil, intended to deliver rapid antidepressant effect from a single infusion.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Dizziness and transient amnesia each affected about one patient in seven in the proof-of-concept trial, and somnolence about one in nine, which is the signature of a drug doing something noticeable to the brain during a 40-minute infusion. That study randomized 70 people and 53 finished it. No distinctive safety signal emerged over six weeks and the compound was reported as well tolerated at both dose levels, with ketamine dosed alongside as an active comparator. The whole human record is that one study, so nothing is settled about repeated infusions over months or about who should not receive it.
History
Developed by Novartis; a Phase II randomized, placebo-controlled proof-of-concept study in treatment-resistant depression (Shelton et al, 2025) reported rapid and sustained efficacy; later-stage development outcome not yet established as of this entry.
Subjective profileweighing the evidence above
Too early to call it a failure or a win; it's the current live test of whether NR2B selectivity can finally deliver where three decades of predecessors came up short.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Is MIJ821 approved for use?
No. As of its 2025 published Phase II results, it remains an investigational compound; it has not completed Phase III testing.
How is it related to older NR2B drugs like eliprodil and traxoprodil?
It targets the same GluN2B subunit of the NMDA receptor through the same general negative-allosteric-modulator strategy, making it the newest link in a research lineage that stretches back to the late 1980s.
Limitations of the evidence
- long-term safety data still limited
- late-stage trial outcome not yet established
Notes and cautions
- IV infusion required