PreclinicalResearch compound

NSI‑189

Hippocampus-selective neurogenesis inducer. Neuralstem Phase 1b/2 clinical trials for depression.

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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

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

Journal of cellular physiology

NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats.

Tajiri N, Quach DM, Kaneko Y, et al.

PMID: 28181668Open
Expert Opin Investig Drugs. 2017;26(5):505-518.

The neurogenic compound NSI-189 phosphate: pro-cognitive and antidepressant effects (review)

Papakostas GI et al.

PMID: 28460574Open

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MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: June 19, 2026

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.