This page describes pharmacological agents that may have legal restrictions, side effects, and drug interactions in your jurisdiction. Information is for educational research only — consult a clinician before considering any compound.

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NSI-189

Well Researched

Synthetic small molecule originally from Neuralstem that genuinely promotes hippocampal neurogenesis in animals (~36-66% volume increase…

Aliases (6)

NSI-189 phosphate · ALTO-100 · amdiglurax · Neuralstem-189 · CAS 1270138-40-3 · NSI-189

TYPICAL DOSE

40 mg/day

Daily

ROUTE

Oral (tablet)

Oral

CYCLE

4-12 weeks on, 2-4 weeks off

As prescribed

STORAGE

Room temp; original container

Room temp

Overview

What is NSI-189?

NSI-189 is a synthetic small-molecule neurogenic agent developed by Neuralstem Inc., investigated as a novel antidepressant and cognitive enhancer. It was in clinical trials for major depressive disorder but did not meet primary efficacy endpoints in Phase 2.

Key Benefits

Reported to stimulate hippocampal neurogenesis in preclinical models, with users anecdotally reporting improvements in mood, memory, and cognitive function. Investigated for MDD, traumatic brain injury, Angelman syndrome, and radiation-induced cognitive impairment.

Mechanism of Action

Promotes proliferation of human hippocampal neural stem cells in vitro and in vivo via mechanisms not yet fully elucidated; appears to work independently of monoaminergic systems. Increases hippocampal volume in animal models without classical antidepressant receptor activity.

▸Brand options5 known

NSI-189 phosphateALTO-100Neuralstem-189CAS 1270138-40-3NSI-189

StatusNot scheduled in US — investigational drug; research-chemical-only outside clinical trials

Research Indications

Most Effective

Half-life ~17.4-20.5 hours

long enough for once-daily dosing, fits 4-5 days to steady state

Peptide Interactions

cerebrolysin

Synergistic

Both target the neurotrophic / neurogenic axis. Cerebrolysin delivers BDNF/NGF/GDNF mimetic activity at TrkA/TrkB receptors; NSI-189 indirectly upregulates B…

semax / n-acetyl-semax-amidate

Synergistic

Both upregulate BDNF; NASA's longer-acting BDNF curve plus NSI-189's neurogenic action are mechanistically complementary. Again, no human evidence.

bpc-157

Synergistic

Broad neuroprotective + neurogenic signal in animal data; theoretical multiplier on whatever NSI-189 is doing at the niche level.

citicoline / alpha-GPC

Synergistic

Cholinergic substrate for new neurons forming new synapses. The canonical stack already has citicoline.

omega-3 DHA

Synergistic

Membrane substrate for new neurons. The canonical stack already has 2 g DHA — no need to add.

dihexa

Avoid

Both promote brain plasticity via different mechanisms (NSI-189 → progenitor proliferation; dihexa → HGF/c-Met synaptogenesis). Stacking compounds two unprov…

High-dose racetams + cholinergics

Avoid

during NSI-189 onset — confounds whether benefit/AE is from NSI-189 or from the stack.

Quality Indicators

✓

Pharmacy-dispensed, intact packaging

Prescription tablets in original sealed packaging from a licensed pharmacy.

Generic vs branded

Generics are usually fine but bioavailability can vary slightly; track if you switch.

✗

Unbranded blister or counterfeit risk

Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.

What to Expect

Day 1
PK-driven acute peak per administration. Verify dose tolerated.
Week 1
Steady-state reached for most daily-dosed pharma.
Week 2-4
Therapeutic effect established; titration window if needed.
Long-term
Periodic monitoring per drug class (labs, BP, ECG as applicable).

Side Effects & Safety

Common (>10% in trials and forum reports): Headache (often resolves within first week in trials, persistent in some research-chem users), nausea, abnormal dreams (Alto Phase 2b explicitly noted this).
Less common (1-10%): Fatigue, dizziness, sleep disruption, mild GI upset, dry mouth, low-grade anxiety, mood lability.
Rare / forum-only (research-chem material): Severe anxiety escalation after 1-2 weeks, neuropathic pain reports, peripheral numbness, paradoxical depressive worsening, "flu-like" malaise. Likely partially attributable to research-chem impurity variance, since clinical-grade material across three trials had clean safety.
Theoretical pro-mitogenic concern: Anything that promotes neural progenitor proliferation has a non-zero theoretical risk of promoting other proliferative processes. The concern is much less acute than for dihexa (which acts on HGF/c-Met, a pathway with explicit cancer involvement), because NSI-189's effect appears restricted to neural progenitor cells in vitro and there's no signal in the trial AE data. But long-term safety is unknown — longest controlled human exposure is months, not years. Anyone with a personal/family history of glioma or other CNS malignancy should avoid.
Specific watch periods: First 1-2 weeks (most adverse responses surface here in research-chem reports). If headache or nausea persists past week 2, discontinue.