NSI-189
NSI-189 phosphate · Neurogenic compound (failed antidepressant)
What it is
A hippocampal-neurogenesis drug candidate that ran real depression trials, missed its primary endpoints, and migrated to research-chem shelves on the strength of its mechanism story and secondary-measure signals.
What human evidence shows
Phase 1 and 2 trials exist and are published — the honest reading is a failed program, not a suppressed success: the Phase 2 trial missed its primary endpoint, and secondary findings were exploratory without a consistent dose-response. The neurogenesis mechanism is validated in animals, unproven as a human therapeutic lever.
Risks
The trial record is short-duration; long-term use has no data. Trial-reported effects were mild (headache, dry mouth), but self-treating mood with an antidepressant-class compound outside any care context — especially alongside other serotonergic or stimulant compounds — is unmonitored psychiatry.
Legal status
US: unapproved, unscheduled; research-chemical market.
Evidence base
early literature
Early human evidence: at least one human trial report, and not much beyond it.
- phase 3/4
- 0
- randomised
- 1
- reviews
- 0
- human trials
- 3
Counts are of published papers, not distinct trials, and measure how much research exists — not whether this works or is safe for you.
Research (12)
- The neurogenic compound, NSI-189 phosphate: a novel multi-domain treatment capable of pro-cognitive and antidepressant effectsExpert Opin Investig Drugs · 2017
- NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorderAnn Clin Psychiatry · 2020
- NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke ratsJ Cell Physiol · 2017
- Enhancement of Mitochondrial Function by the Neurogenic Molecule NSI-189 Accompanies Reversal of Peripheral Neuropathy and Memory Impairment in a Rat Model of Type 2 DiabetesJ Diabetes Res · 2022
- Enhancement of synaptic plasticity and reversal of impairments in motor and cognitive functions in a mouse model of Angelman Syndrome by a small neurogenic molecule, NSI-189Neuropharmacology · 2019
- Amelioration of Both Central and Peripheral Neuropathy in Mouse Models of Type 1 and Type 2 Diabetes by the Neurogenic Molecule NSI-189Diabetes · 2019
- A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorderMol Psychiatry · 2020
- Remediation of Radiation-Induced Cognitive Dysfunction through Oral Administration of the Neuroprotective Compound NSI-189Radiat Res · 2018
- A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patientsMol Psychiatry · 2016
- A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patientsMol Psychiatry · 2016
- Neuroprotective efficacy of P7C3 compounds in primate hippocampusTransl Psychiatry · 2018
- Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in miceAging (Albany NY) · 2023
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