Appearance:white to off-white solid powder
Purity: > 98%
NSI-189(cas 1270138-40-3) is a nootropic and neurogenic research chemical derived from nicotinamide and pyrazine created by Neuralstem, Inc. NSI-189 has been shown to stimulate neurogenesis of human hippocampus-derived neural stem cells in vitro and in vivo. NSI-189 has been shown to increase the hippocampal volume of healthy adult mice by 20%. NSI-189 successfully completed a phase 1 clinical trial in 2011 where it was administered to 41 healthy volunteers, with no adverse effects reported. A phase 1B clinical trial for treating major depressive disorder in 24 patients started in 2012, with study completion expected in January 2014. Assuming positive outcomes in the phase 1b clinical trial, Neuralstem intends to pursue further clinical trials for a variety of encephalopathic conditions including major depressive disorder, traumatic brain injury, Alzheimer/'s disease, post-traumatic stress disorder, troke and natural aging.
Developer Palisade Bio; University of California, San Diego
Class Antidepressants; Antihyperglycaemics; Neuroprotectants; Nootropics; Piperazines; Pyridines; Small molecules; Vascular disorder therapies
Mechanism of Action Neurogenesis stimulants
Orphan Drug StatusYes - Angelman syndrome
New Molecular Entity Yes
Available For Licensing Yes
1. Ann Clin Psychiatry. 2020 Aug;32(3):182-196.
NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately
depressed patients: A post-hoc analysis of a phase 2 study of major depressive
Johe KK, Kay G, Kumar S, Burdick KE, McIntyre RS, Papakostas GI, Fava M.
BACKGROUND: NSI-189 phosphate (NSI-189) is a novel neurogenic molecule with
pleiotropic properties, including antidepressant, procognitive, synaptoplastic,
and neurotrophic activities demonstrated in preclinical studies. Its
antidepressant activity is monoamine-independent. NSI-189 was previously tested
in patients with recurrent major depressive disorder in an inpatient setting.
METHODS: This study involved 220 patients randomized to an NSI-189 40-mg dose,
NSI-189 80-mg dose, or placebo daily for 12 weeks. The study utilized the
sequential parallel comparison design, in which the drug effect was tested in 2
separate stages of 6 weeks each. Herein, post-hoc analyses of the data are
RESULTS: NSI-189's antidepressant effect increased when the participants'
initial baseline depression severity was dichotomized along a Montgomery-Åsberg
Depression Rating Scale (MADRS) score of 30. The NSI-189 80-mg dose showed
significant benefit over placebo when utilizing the MADRS-6 (P = .046) in the
subgroup of patients who were moderately depressed (MADRS < 30) but was not
significant in patients who were severely depressed (MADRS ≥30). More pronounced
procognitive effects were also observed in the moderate subgroup relative to the
severe subgroup or the whole study group, in which 11/36 (31%), 5/36 (14%), or
7/36 (19%) of CogScreen variables significantly improved, respectively.
CONCLUSIONS: These results suggest that NSI-189 is effective as a safe
adjunctive therapy, with most compelling antidepressant and procognitive
benefits noted in patients with moderate depression.