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 Pramiracetam — 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.
Pramiracetam is a non-peptide synthetic racetam-class nootropic (2-oxopyrrolidone/pyrrolidinone acetamide derivative) with CAS 68497-62-1 and molecular formula C14H27N3O2. It was previously approved and marketed in Italy and some Eastern European countries under brand names Pramistar, Neupramir, and Remen for memory/attention deficits in aging-associated dementias; Italian authorization was revoked in 2020 at manufacturer request. It is not FDA-approved in the United States, where it is sold only as an unapproved gray-market research chemical. The related racetam phenylpiracetam is explicitly listed on the WADA Prohibited List as an S6 stimulant; pramiracetam itself is not explicitly named, leaving its status under WADA's 'similar structure/effect' catch-all unresolved.
NSI-189
Pramiracetam
Category
Legal Status
Mechanism
Side Effects
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NSI-189
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Check NSI-189 prices →Pramiracetam
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Check Pramiracetam prices →COA corpus from Disclosed Labs — independently tested batches only.
NSI-189
No COA data yet.
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2
COAs
99.9%
Avg purity
2
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
Human data consist of a handful of small older trials (1985–1996): healthy-volunteer pharmacokinetic studies, a scopolamine-induced-amnesia challenge study, a placebo-controlled trial in young males with head-injury/anoxia-related memory deficits (400 mg TID improved delayed recall), and a small dose-finding trial in Alzheimer's disease that found no convincing benefit at doses up to 4,000 mg. A scopolamine-challenge study (600 mg BID × 10 days) showed partial mitigation of induced amnesia in healthy young and older male volunteers. No modern (post-2000) randomized controlled trials were located. Preclinical findings: in rats, 7.5 and 15 mg/kg/day × 7 weeks significantly improved reference (long-term) memory on a 16-arm radial maze but did not affect working memory; 300 mg/kg i.p. increased cortical nitric oxide synthase activity ~20% (synergistic ~40% increase with lithium pretreatment); moderate protection against hypobaric-hypoxia-induced deficits in immature rats.
NSI-189 and Pramiracetam 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
Disclosed Labs