Rislenemdaz
nmda modulator · intended antidepressant effect via nr2b blockade class / nmda modulatorspec sheet6 rows
Rislenemdaz began life at Merck as MK-0657, an orally bioavailable, highly selective GluN2B (NR2B) subunit NMDA receptor antagonist, first explored in small studies for Parkinson's disease before its antidepressant potential drew attention. Merck eventually licensed it to the smaller company Cerecor, which renamed it CERC-301 and advanced it into Phase II testing as an adjunctive treatment for treatment-resistant depression. The trial did not meet its primary endpoint, and Cerecor deprioritized the depression program in the late 2010s. The compound, now most often referenced as rislenemdaz, has since lived on mainly in preclinical mechanistic research, including studies tracing its antidepressant-like effects to the lateral habenula.
- oral dosing (no infusion)
- high receptor selectivity for GluN2B
- strong preclinical antidepressant-like signal
- did not meet primary endpoint in Phase II depression trial
- Before it was tested for depression, MK-0657 was first studied in small trials for Parkinson's disease.
- A 2020 preclinical study traced its antidepressant-like effects specifically to the lateral habenula, a brain region increasingly implicated in depression and reward processing.
Mechanism
Orally bioavailable, highly selective GluN2B (NR2B) subunit , designed to isolate the antidepressant-relevant subtype from more broadly distributed GluN2A-containing receptors.
Safetyrisks and cautions, not medical advice
Oral dosing at 4 to 8 mg a day for twelve days produced no dissociative reactions and nothing serious in the small crossover study run at the NIH, which is the entire point of picking the GluN2B subunit instead of blocking the channel outright. That study completed only five patients, so it proves little on its own. Preclinical safety pharmacology and neurotoxicity work turned up nothing specific, although rats became hyperactive once receptor occupancy passed roughly 75 percent, which hints at where the useful window ends. The larger trial that followed missed its endpoint and its safety data was never published.
History
Discovered at Merck as MK-0657; licensed to Cerecor and renamed CERC-301; advanced into Phase II adjunctive treatment-resistant depression trials in the mid-2010s, which failed to meet the primary endpoint, and the program was deprioritized.
Subjective profileweighing the evidence above
Another NR2B-selective candidate that worked cleanly in rodent depression models but couldn't clear the human efficacy bar, part of a long pattern for this receptor subtype.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Why does this compound have three different names?
It moved between companies: discovered at Merck as MK-0657, licensed and renamed CERC-301 by Cerecor, and later referred to by the name rislenemdaz in the scientific literature.
Is it still in development?
Not for depression. Cerecor deprioritized the program after the Phase II trial missed its primary endpoint; the compound now mainly appears in academic preclinical research.
Limitations of the evidence
- limited published human safety data
Adverse effects
- did not meet primary endpoint in Phase II depression trial