NSi-189 powder (1270138-40-3)

NSI-189 powder is an experimental antidepressant. Neuralstem, Inc. is currently testing it for use in major depression, in addition to treating cognitive impairments, and brain degeneration. It may induce specific brain regeneration

NSI-189 is most likely selective only to two nervous system controlling regions in the brain (hippocampus, subventricular zone)

Pharma companies used to love antidepressants. Millions of people are depressed. Millions of people who aren’t depressed think they are. So they poured money into antidepressant research, culminating in 80s and 90s with the discovery of selective serotonin reuptake inhibitors (SSRIs) like Prozac. Since then, research has moved into exciting new areas, like “more SSRIs”, “even more SSRIs”, “drugs that claim to be SNRIs but on closer inspection are mostly just SSRIs”, and “drugs that claim to be complicated serotonin modulators but realistically just work as SSRIs”The study will consist of a screening period and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80 milligrams/day (provided as 40 milligrams twice per day), NSI-189 40 milligrams once a day, or placebo.

NSI‐189‐treated animals revealed significant increments in neurite outgrowth as evidenced by MAP2 immunoreactivity that was prominently detected in the hippocampus and partially in the cortex. These results suggest NSI‐189 actively stimulated remodeling of the stroke brain. Parallel in vitro studies further probed this remodeling process and demonstrated that oxygen glucose deprivation and reperfusion (OGD/R) initiated typical cell death processes, which were reversed by NSI‐189 treatment characterized by significant attenuation of OGD/R‐mediated hippocampal cell death and increased Ki67 and MAP2 expression, coupled with upregulation of neurogenic factors such as BDNF and SCF.

NSI-189 is a benzylpiperizine-aminiopyridine, a novel chemical entity that stimulates neurogenesis of human hippocampus-derived neural stem cells in vitro and stimulates neurogenesis in murine hippocampus in vivo. Emerging evidence also indicates that NSI-189 phosphate has regionally specific effects insofar as neurogenesis is observed largely in the subventricular zone of the hippocampus. Results from a preliminary proof of concept study suggests that NSI-189 may be capable of mitigating depressive symptoms and improve cognitive function in adults with DSM-5-defined Major Depressive Disorder (MDD). Expert opinion: Preliminary proof-of-concept studies indicate both antidepressant and procognitive effects. Beneficial effects in cognitive-emotional processing as well as whether the procognitive effects are independent of antidepressant effects are vistas of future research. Taken together, NSI-189 is a multi-domain neurogenic compound with brain-therapeutic properties with potential therapeutic applications across disparate psychiatric disorders.

NSI‐189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti‐depressant drug in a clinical trial and being tested in a Phase 2 efficacy trial for treatment of major depression. Oral administration of NSI‐189 in adult Sprague–Dawley rats starting at 6 hr after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke‐induced motor and neurological deficits, which was maintained up to 24 weeks post‐stroke. Histopathological assessment of stroke brains

COA

1.  Fava M, Johe K, Ereshefsky L, Gertsik LG, English BA, Bilello JA, Thurmond LM, Johnstone J, Dickerson BC, Makris N, Hoeppner BB, Flynn M, Mischoulon D, Kinrys G, Freeman MP. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016 Oct;21(10):1372-80. doi: 10.1038/mp.2015.178. PubMed PMID: 26643541; PubMed Central PMCID: PMC5030464.
2.  Fava M, Johe K, Ereshefsky L, Gertsik LG, English BA, Bilello JA, Thurmond LM, Johnstone J, Dickerson BC, Makris N, Hoeppner BB, Flynn M, Mischoulon D, Kinrys G, Freeman MP. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016 Oct;21(10):1483-4. doi: 10.1038/mp.2016.140. PubMed PMID: 27528461; PubMed Central PMCID: PMC5030463