PreclinicalHuman trials

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

NSI-189 structure

Molecular Formula

C22H30N4O

Molecular Weight

366.50 g/mol

IUPAC Name

(4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)-3-pyridinyl]methanone

PubChem CID

50922681

Where does NSI-189 sit?

See how this peptide compares across all 70 peptides in our database.

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

Headache (common in clinical trials)Vivid dreams (common)Mild cognitive side effects in some users — brain fog paradoxically (uncommon)Emotional blunting (uncommon)

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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