NSI-189 is a small molecule developed by Neuralstem and given the international name amdiglurax.
Amounts reported for NSI-189 are listed under Reported protocols, each with its source and study kind. No amount ladder is inferred from them. This is educational source context, not a protocol or recommendation.
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What published studies and recent community write-ups report about amounts, timing and course length. 4 clinical, 2 preclinical and 1 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Clinical4 rows | |||||
| Phase 1B multiple-dose escalation in depression24 inpatients with major depressive disorder, 6 on drug and 2 on placebo in each of three cohorts | 40 mg once daily, 40 mg twice daily or 40 mg three times daily | Once, twice or three times daily by cohort | Oral | 28 days inpatient, with outpatient follow-up to day 84None described | Molecular Psychiatry (PubMed Central)2016 |
| Tolerated at all three schedules with no serious adverse effects, and exposure rose roughly in proportion to dose with a half-life of 17.4 to 20.5 hours. Depression and cognitive scales moved in the drug's favour with medium to large effect sizes that persisted into follow-up, but each cohort held only eight people, which the authors name as the main limitation. | |||||
| Phase 2 monotherapy trial in major depressive disorder220 outpatients with major depressive disorder, aged 18 to 60 | 40 mg daily or 80 mg daily | Once daily | Oral | 12 weeks, run as two 6-week stagesNone described | Molecular Psychiatry (PubMed Central)2020 |
| The primary endpoint, the clinician-rated Montgomery-Asberg depression scale, did not separate from placebo at either dose. The 40 mg arm did better than placebo on patient-rated depression and cognitive-functioning questionnaires and on some objective cognitive tests, and both doses were well tolerated. A trial that misses its primary endpoint cannot be read as a positive result, whatever the secondary measures show. | |||||
| Post-hoc analysis of the Phase 2 data by baseline severityThe same 220 Phase 2 patients, split at a baseline depression score of 30 | 80 mg daily (the arm that showed the post-hoc benefit) | Once daily | Oral | 12 weeksNone described | Annals of Clinical Psychiatry (PubMed)2020 |
| In the moderately depressed subgroup the 80 mg dose beat placebo on a six-item version of the depression scale, and more cognitive variables improved than in the severe subgroup or the whole sample. These are post-hoc subgroup findings from a trial that missed its primary endpoint, so they generate a hypothesis rather than settle one. | |||||
| Phase 2 trial registration220 adults aged 18 to 60 with major depressive disorder | 40 mg or 80 mg daily against placebo | Once daily | Oral | The registered study ran from March 2016 to December 2017None described | ClinicalTrials.gov2016 |
| The registry record carries the trial design and arms but no posted results, and its status is listed as unknown. It is the only Phase 2 study of this compound on the register. | |||||
| Preclinical2 rows | |||||
| Rat model of ischaemic stroke48 adult male Sprague-Dawley rats after middle cerebral artery occlusion | 30 mg/kg, calculated on the active base rather than the phosphate salt | Once daily | Oral gavage, starting 6 hours after the stroke | 12 weeks of dosing, with follow-up to 24 weeksNot applicable | Journal of Cellular Physiology (PubMed Central)2017 |
| Motor and neurological deficits improved and the gain held to 24 weeks, with more neurite outgrowth in hippocampus and cortex on histology. Companion cell work showed protection against oxygen-glucose deprivation with higher BDNF and stem cell factor. All of this is rat and cell data. | |||||
| Radiation-induced cognitive dysfunction in ratsLong-Evans rats, 15 to 16 per group, after 27 Gy of fractionated head-only irradiation | 30 mg/kg | Once daily | Oral gavage at 2 mL/kg | 4 weeksCognition was retested one month after dosing stopped | Radiation Research (PubMed Central)2018 |
| Treated animals performed better on four of five exploration tasks, and the benefit was still present a month after the drug was withdrawn, alongside more new neurons and fewer activated microglia. Hippocampal volume did not change. These are rat endpoints in a radiation model, not a human indication. | |||||
| Community-reported1 row | |||||
| Vendor capsule product | 20 mg per capsule, 60 capsules per bottle (1,200 mg total) | Not stated | Oral capsule | Not stated | Community resource2026 |
| A vendor claim about what ships, not a protocol. The per-capsule amount is half the 40 mg daily dose used in both trials, which is the only connection between this product format and the published work. The listing states the material is not for human use. | |||||
Plus 2 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.
NSI-189 is a small molecule developed by Neuralstem and given the international name amdiglurax, selected because it stimulates the growth of new neurons from human hippocampal stem cells in culture and in mouse hippocampus, rather than by acting on monoamine reuptake like conventional antidepressants. It was dosed as the phosphate salt in two placebo-controlled trials in major depressive disorder: a 24-patient Phase 1B at 40 mg once, twice or three times daily for 28 days, and a 220-patient Phase 2 at 40 or 80 mg daily for 12 weeks. The Phase 2 missed its primary depression-rating endpoint while patient-rated and cognitive measures favoured the drug, and no product has been approved anywhere.
These themes describe recurring questions in published research. They are not claims of effectiveness or recommendations for use.
Neuroplasticity, cognition, stress and sleep models.
Tolerated at all three schedules with no serious adverse effects, and exposure rose roughly in proportion to dose with a half-life of 17.4 to 20.5 hours. Depression and cognitive scales moved in the drug's favour with.
The primary endpoint, the clinician-rated Montgomery-Asberg depression scale, did not separate from placebo at either dose. The 40 mg arm did better than placebo on patient-rated depression and cognitive-functioning.
In the moderately depressed subgroup the 80 mg dose beat placebo on a six-item version of the depression scale, and more cognitive variables improved than in the severe subgroup or the whole sample. These are post-hoc.
The registry record carries the trial design and arms but no posted results, and its status is listed as unknown. It is the only Phase 2 study of this compound on the register.
Motor and neurological deficits improved and the gain held to 24 weeks, with more neurite outgrowth in hippocampus and cortex on histology. Companion cell work showed protection against oxygen-glucose deprivation with.
Study models remain visible so laboratory and animal findings are not mistaken for established human outcomes.
4 protocol rows on this page come from human trials, trial registrations, regulator labels or reviews of human data. Approval status and populations are stated per row.
2 protocol rows describe animal, cell or toxicology work. Amounts from these rows do not translate to people.
1 row record what blogs, vendor write-ups or forums describe for NSI-189. None has been verified against primary literature.
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
NSI-189 phosphate, Amdiglurax, (4-benzylpiperazin-1-yl)(2-(isopentylamino)pyridin-3-yl)methanone, UNII YVE9U408ZL, CHEMBL4302505, DTXSID901025668, HY-13999
DYTOQURYRYYNOR-UHFFFAOYSA-N
(4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)-3-pyridinyl]methanone
7 curated references, each with its journal, year and study model, plus 2 community resources reported but not linked.