Decoglurant
glutamatergic · intended adjunctive antidepressant effect class / glutamatergicspec sheet6 rows
Decoglurant took a different route into the same glutamate story that ketamine made famous: instead of blocking the NMDA receptor directly, it dials down mGlu2 and mGlu3, presynaptic autoreceptors that normally put the brakes on glutamate release. Turn those autoreceptors down and glutamate signaling goes up, in theory reproducing some of the downstream synaptic effects tied to ketamine's antidepressant action without ever touching the NMDA channel. Roche ran a randomized, placebo-controlled Phase II trial (published 2020) testing decoglurant as an 8-week add-on across three doses in patients with partially treatment-resistant depression. None of the doses beat placebo on the primary MADRS endpoint, and Roche discontinued the program, closing off mGlu2/3 negative allosteric modulation as a standalone antidepressant strategy, at least for now.
- no direct NMDA receptor engagement (theoretically lower dissociation risk)
- well-controlled dose-ranging Phase II design
- clear negative data that helped narrow the field
- Decoglurant never touches the NMDA receptor at all; its entire antidepressant hypothesis rested on indirectly boosting glutamate release by blocking the receptors that normally suppress it.
Mechanism
Negative modulator at metabotropic receptors mGlu2 and mGlu3; reduces autoreceptor-mediated inhibition of glutamate release, an indirect way of amplifying signaling.
Safetyrisks and cautions, not medical advice
Of the 357 patients randomized in the Phase II trial, 310 finished the full six weeks, nobody died and serious adverse events were rare, which is about as clean a tolerability result as an adjunctive antidepressant trial produces. Decoglurant was described as well tolerated overall, and the reason it stopped is that it did nothing, not that it did harm. The limits are the ordinary ones for a compound abandoned at this stage: six weeks is the longest anyone has taken it, the 30 mg arm held only 55 patients, and what prolonged mGlu2/3 blockade does to a person remains untested.
History
Developed by Roche; tested in a randomized, double-blind, placebo-controlled Phase II adjunctive depression trial (published 2020, Journal of Clinical Psychiatry) across three fixed doses; discontinued after the trial missed its primary endpoint.
Subjective profileweighing the evidence above
A clean negative result for the indirect glutamate release route to antidepressant effect, useful mainly for ruling the approach out.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Is decoglurant related to basimglurant?
They're both Roche mGluR-targeting compounds studied for depression around the same era, but basimglurant is an mGlu5 negative allosteric modulator while decoglurant targets mGlu2/3; different receptors, similar strategic bet.
Why did Roche stop developing it?
Its Phase II adjunctive depression trial, run across three doses, failed to separate from placebo on the primary MADRS outcome.
Limitations of the evidence
- no efficacy signal over placebo at any tested dose
- limited safety data beyond Phase II