NSI-189
NSI-189 Phosphate
Overview
NSI-189 is a synthetic aminopyridine-benzylpiperazine compound originally developed by Neuralstem Inc that has demonstrated neurogenic properties in the hippocampus and antidepressant effects in clinical trials. It completed a Phase 1b trial for major depressive disorder and a Phase 2 trial that showed improvements in cognitive function though with mixed results on the primary depression endpoint. NSI-189 is notable in the research community for subjective reports of significant improvements in mood memory emotional processing and cognitive clarity that have made it one of the most discussed experimental neurological compounds.
Compound Data
Molecular Formula
C22H30N4O
Molecular Weight
366.50 g/mol
IUPAC Name
(4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)-3-pyridinyl]methanone
PubChem CID
50922681Where does NSI-189 sit?
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Mechanism of Action
NSI-189 stimulates neurogenesis in the human hippocampus through mechanisms that are not yet fully characterized but appear to involve direct effects on neural stem cell proliferation and differentiation independent of classic neurotrophic factor pathways. In the Phase 1b trial participants showed increased hippocampal volume on MRI — a rare finding for any pharmacological intervention and a strong indicator of genuine neurogenic activity. NSI-189 also modulates serotonergic signaling and has been shown to increase synaptic density in hippocampal regions. The antidepressant effects may be mediated through both neurogenesis-dependent mechanisms similar to how SSRIs are thought to work long-term and more immediate effects on monoamine neurotransmission.
Dosage Information
Typical Dose
40-80 mg daily
Frequency
Once or twice daily
Administration
Oral capsule
Notes
Phase 1b used 40mg and 80mg daily doses. Research community typically uses 40mg daily. Cycles of 8-12 weeks with breaks recommended.
Potential Side Effects
Community Experiences
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Quick Facts
- Administration
- Oral capsule
- Typical Dose
- 40-80 mg daily
- Frequency
- Once or twice daily
- References
- 0 curated + 1 from PubMed
- Clinical Trials
- 4 registered
- Evidence Score
- 34.3 / 100