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 Alpha-GPC (L-alpha-glycerylphosphorylcholine / choline alfoscerate) and NSI-189 — mechanism, dosing, side effects, legal status, and pricing.
Alpha-GPC is a non-peptide choline-containing phospholipid derivative that serves as an acetylcholine precursor. It is not FDA-approved in the United States, where it is sold as an unregulated dietary supplement and nootropic ingredient. The compound is marketed as a prescription drug in some countries (e.g., Italy as Gliatilin) for cognitive and vascular disorders, though current regulatory approval status has not been confirmed against primary agency databases. Alpha-GPC is not identified as a WADA-prohibited substance in secondary sources.
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.
Alpha-GPC (L-alpha-glycerylphosphorylcholine / choline alfoscerate)
NSI-189
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Alpha-GPC (L-alpha-glycerylphosphorylcholine / choline alfoscerate)
NSI-189
No pricing data yet.
Check NSI-189 prices →Human data: A 12-week randomized controlled trial in 100 subjects with amnestic mild cognitive impairment found 600 mg/day improved ADAS-cog scores by 2.34 points versus placebo with no serious adverse events. A single-blind RCT in 39 healthy volunteers showed 400 mg/day for 2 weeks increased self-reported motivation versus placebo. A small crossover study in 7 resistance-trained men (published only as a conference-supplement abstract) reported a single acute 600 mg dose increased post-exercise growth hormone and peak bench-press force versus placebo. A large retrospective Korean cohort study (n=12,008,977 adults ≥50) found chronic alpha-GPC use associated with elevated 10-year stroke risk (total stroke adjusted HR 1.43, ischemic stroke aHR 1.34) in a dose-dependent pattern. Preclinical: Rat studies showed increased hippocampal acetylcholine release, modulation of choline acetyltransferase/acetylcholinesterase activity in aged rats, attenuation of age-related brain structural changes, and increased hippocampal neurogenesis in seizure models.
Key references
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.
Alpha-GPC (L-alpha-glycerylphosphorylcholine / choline alfoscerate) and NSI-189 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.
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