NSI‑189
Hippocampus-selective neurogenesis inducer. Neuralstem Phase 1b/2 clinical trials for depression.
Pharmacology
Contents
WHAT IS NSI-189?
Detailed overview
NSI-189 is a benzylpiperazine-aminopyridine derivative developed by Neuralstem Inc. as a hippocampus-selective neurogenesis inducer. Phase 1b/2 clinical trials have been conducted in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The mechanism is incompletely understood, but it induces proliferation and differentiation of neuronal progenitor cells in the subgranular zone of the hippocampus. It does not act on known monoamine receptors, independent of the SSRI/SNRI mechanism.
Mechanism
Hippocampal neurogenesis
Half-life
17-20 hours
Onset
1-2 weeks (subjective), 4-6 weeks (plateau)
Legal status
USA research, FDA Phase 2
Receptor profile
- TLX / NR2E1 nuclear receptorStrong
- Hippocampal neurogenesisStrong
- BDNFModerate
- PI3K/Akt/mTOR signalingModerate
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Early irritability, mood agitation (typically in the first week)
- Insomnia, disrupted sleep (avoid late-evening dosing)
- Headache, mild anxiety (anecdotal reports)
- Higher doses (80+ mg) bring more side effects, not stronger benefit (bell-shaped curve)
- Limited human safety data, full side-effect spectrum unknown
- Long half-life (17-20 h) gives cumulative effect, steady state in 4-5 days
Contraindications · 6
- Pregnancy, breastfeeding (no clinical safety data)
- Avoid combining with MAOIs (preclinically untested monoaminergic interaction)
- SSRI/SNRI combination only under medical supervision (serotonin syndrome risk)
- Bipolar spectrum: mania risk, medical monitoring required
- Active psychotic disorder (neurogenesis-inducing mechanism may worsen symptoms)
- Caution with CNS depressants (alcohol, benzodiazepines); not FDA-approved, unknown long-term safety
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats.
Tajiri N, Quach DM, Kaneko Y, et al.
The neurogenic compound NSI-189 phosphate: pro-cognitive and antidepressant effects (review)
Papakostas GI et al.
FAQ
FAQ
NSI-189 is an experimental, still-researched substance that has mainly been studied in clinical trials for depression, with the unusual feature that it is said to stimulate regrowth in the brain's memory-related region, the hippocampus. Trials have observed benefits for mood as well as cognitive functions like memory and learning, and interestingly the effects may persist after stopping the treatment, since the change is described as structural rather than immediate. Because this is still a substance in development rather than an approved medicine, human experience with it remains limited to clinical trial settings.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.