NSI-189
NSI-189 is a synthetic small-molecule neurogenic compound (marketed under a peptide-adjacent research-chemical label) originally developed by Neuralstem as a clinical-stage antidepressant/pro-cognitive candidate; its Phase 2 trial for major depressive disorder failed to meet its primary endpoint, and the compound is now being developed under a new code name, ALTO-100, by Alto Neuroscience.
This page is a research-orientation summary, not a dosing guide. For anything beyond general background, read the primary literature or talk to a qualified clinician — specifics like amount, frequency, or administration aren't something we publish here.
What it does & how it works
NSI-189 was designed as a neurogenic compound intended to promote proliferation and maturation of hippocampal neural progenitor cells, with proposed downstream effects on hippocampal volume and synaptic connectivity relevant to mood and cognition. Preclinical studies also report effects on mitochondrial function and reversal of neuropathy-related deficits in diabetic rodent models, suggesting effects beyond hippocampal neurogenesis alone, though the precise molecular target has not been definitively established in the public literature.
Typical results seen in research
In a randomized, double-blind, placebo-controlled Phase 2 trial in outpatients with major depressive disorder, NSI-189 did not achieve statistically significant improvement over placebo on its primary endpoint (MADRS score reduction) at either dose tested, though a post-hoc analysis suggested a possible benefit in moderately (but not severely) depressed patients and on some self-report and cognitive measures. Given the failed primary endpoint and reliance on post-hoc/secondary findings, NSI-189 should be described as having preliminary, mixed, and ultimately inconclusive clinical evidence rather than as a validated antidepressant or cognitive-enhancement agent. Development of the molecule has continued under Alto Neuroscience as ALTO-100, including a registered Phase 2b trial in bipolar depression, so the original NSI-189 program should not be described as abandoned.
How it’s commonly used
In its published clinical trials, NSI-189 (as NSI-189 phosphate) was administered orally in capsule form.
- Molecular Psychiatry · 2020 A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder
- Annals of Clinical Psychiatry · 2020 NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder
- Expert Opinion on Investigational Drugs · 2017 The neurogenic compound, NSI-189 phosphate: a novel multi-domain treatment capable of pro-cognitive and antidepressant effects
Curated from published literature for research orientation. Not an exhaustive review, and not a substitute for reading primary sources.