Lanicemine
nmda modulator · may lift depressed mood within hours (trial setting) class / nmda modulatorspec sheet6 rows
Lanicemine (AZD6765) was built on a simple idea: if ketamine's antidepressant effect comes from blocking NMDA receptors, maybe a low-trapping blocker that unbinds from the channel faster than ketamine could deliver the mood lift without the dissociation. NIMH researchers ran an early single-infusion proof-of-concept study that supported the idea, and AstraZeneca picked it up for a multi-dose adjunctive depression program in the mid-2010s. Two placebo-controlled trials followed, then a larger Neuropsychopharmacology-published study in patients with a history of inadequate antidepressant response; none of them separated cleanly from placebo on the primary endpoint, despite the promising early signal. AstraZeneca quietly closed the program around 2015, and lanicemine became a cautionary tale about how much the trapping-rate theory alone could explain.
- low dissociation relative to ketamine in trial dosing
- fast onset window in early studies
- IV dosing allowed tight PK control
- informed later low-trapping NMDA drug design
- dizziness
- paresthesia
- An early single-dose NIMH study showed antidepressant signal without dissociation, which is what got AstraZeneca interested in the first place.
- Despite the negative Phase II results, lanicemine is still used in academic imaging studies (like anterior cingulate cortex research) as a comparison tool against ketamine.
Mechanism
Low-trapping, use-dependent channel blocker; unlike ketamine, it dissociates from the open channel quickly, which was meant to limit the dissociative and psychotomimetic side effects tied to prolonged channel block.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Roughly 300 patients received fifteen intravenous infusions over twelve weeks, which makes this one of the better characterised failed drugs of its generation. Dizziness was the commonest complaint and was always mild or moderate; serious events were slightly less frequent on drug than on placebo. Dissociative events reached 11 percent at the 100 mg dose against 4 percent on placebo, all mild, and across the whole study only one event was judged genuinely psychotomimetic. Blood pressure rose briefly during infusions, orthostatic drops were more common on drug, and cognitive testing, electrocardiograms and blood work showed nothing.
History
Discovered at AstraZeneca; tested by NIMH (Zarate lab) as a single-infusion proof-of-concept, then advanced by AstraZeneca through Phase II adjunctive depression trials in the mid-2010s before being discontinued for lack of efficacy.
Subjective profileweighing the evidence above
A well-designed test of the trapping-rate hypothesis that came back negative, which made it a genuinely useful negative result for the field.
Resources
This entry is here for reference.
Research
- 1.Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study
- 2.Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate
2 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Is lanicemine available anywhere today?
No. AstraZeneca discontinued the depression program after Phase II trials failed to beat placebo, and it was never sold or prescribed.
How is it different from ketamine?
Both block the NMDA receptor channel, but lanicemine unbinds from the channel much faster (low-trapping), which was designed to reduce dissociation; it did not, however, match ketamine's antidepressant effect size in later trials.
Limitations of the evidence
- did not separate from placebo on efficacy in later trials
- limited long-term safety data (program halted early)
Adverse effects
- dizziness
- paresthesia