Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of NSI-189 and Sunifiram — mechanism, side effects, legal status, and pricing.
NSI-189 (INN: amdiglurax; developmental code ALTO-100) is a non-peptide small-molecule benzylpiperazine-aminopyridine derivative investigated as a neurogenic/neuroplasticity-modulating agent for major depressive disorder. It stimulates hippocampal neural progenitor proliferation and differentiation in vitro and neurogenesis in vivo (mouse), acting independently of monoamine reuptake pathways. NSI-189 has never been FDA-approved; Phase 2 monotherapy trials in MDD (220 patients, 2020) and a Phase 2b trial under Alto Neuroscience (~300 patients, 2024) both failed to meet primary MADRS endpoints, and it remains investigational only.
Sunifiram (DM-235) is a synthetic non-peptide piperazine derivative marketed online as an 'ampakine-like' cognitive enhancer. Despite common branding, primary research shows it acts indirectly via the glycine-binding site of the NMDA receptor to potentiate AMPA-receptor-mediated transmission, not as a direct AMPA agonist. No human clinical trials or toxicology studies have been conducted, and sunifiram is not approved for any human or veterinary use worldwide. It is sold on the gray market without regulatory vetting.
NSI-189
Sunifiram
Category
Legal Status
Mechanism
Side Effects
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
NSI-189
No pricing data yet.
Check NSI-189 prices →Sunifiram
COA corpus from Disclosed Labs — independently tested batches only.
NSI-189
No COA data yet.
Submit testing data →Sunifiram
1
COAs
99.5%
Avg purity
1
Labs
Human data exist from three registered trials: a Phase 1 single-dose PK study in healthy volunteers (NCT01310881), a Phase 1B multiple-dose-escalation study in 24 MDD patients (28-day inpatient dosing at 40 mg once/twice/thrice daily; half-life ~17.4–20.5 hours; no serious adverse events; no significant hippocampal volume change at day 28 or 84), and a Phase 2 double-blind, placebo-controlled trial in 220 MDD outpatients (12 weeks at 40 mg or 80 mg daily) that missed its primary MADRS endpoint at both doses (p=0.22 and p=0.34, respectively), with some significant secondary/patient-reported benefits at 40 mg. A Phase 2b trial under the ALTO-100 designation (~300 adults, 34 US sites, 6-week double-blind) also failed to meet its primary MADRS endpoint (topline October 2024). Preclinical findings include improved motor/neurological deficits sustained to 24 weeks in a rat stroke model (oral dosing starting 6 hours post-MCAO; increased hippocampal/cortical MAP2 neurite outgrowth; in vitro OGD/R assays showed reduced cell death and upregulated BDNF/SCF), reversal of motor and cognitive impairments in an Angelman syndrome mouse model (with mild performance enhancement in wild-type mice), improved Barnes maze memory retention in a 5xFAD Alzheimer's mouse model (conference abstract), and prevention of peripheral neuropathy indices with increased hippocampal neurogenesis/synaptic markers/volume and protected long-term memory in mouse and rat models of type 1 and type 2 diabetes, alongside enhanced mitochondrial function in a type 2 diabetic rat model.
Key references
No human data exist. In olfactory-bulbectomized mice given oral sunifiram 0.01–1.0 mg/kg daily for 7–12 days, spatial reference memory (Y-maze) and short-term recognition memory (novel object recognition) improved, and impaired hippocampal CA1 long-term potentiation was restored via NMDAR-glycine-site-dependent CaMKII/PKC signaling (blocked by gavestinel). In mouse hippocampal slices, sunifiram (1–1000 nM, peaking at 10 nM with a bell-shaped dose-response) potentiated CA1 LTP via the glycine-site/PKCα/CaMKII pathway. In passive-avoidance models, sunifiram reversed amnesia in mice and rats at doses roughly four orders of magnitude lower than piracetam. No toxicology studies or human clinical trials have been conducted as of 2016.
NSI-189 and Sunifiram are both in the Cognitive category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Contraindications
Lab Testing
Key references
Disclosed Labs