Modalert and Modvigil both contain modafinil. Sun Pharma lists Modalert in its Indian product catalog, while HAB Pharmaceuticals lists Modvigil. At the same labeled strength, the stated amount of active ingredient is the same. The useful comparison is therefore the specific formulation, manufacturer, dispensing source and cost.[1][2]
This guide compares the ordinary oral tablets. HAB also lists a separate Modvigil MD product, so check the complete product name when comparing packaging.
Modalert vs Modvigil at a Glance
The manufacturers' catalogs identify both brands as modafinil tablets. Here are the product details that separate their listings.
Feature
Modalert
Modvigil
Company
Sun Pharma
HAB Pharmaceuticals
Active ingredient
Modafinil
Modafinil
Listed standard strengths
100 mg and 200 mg
100 mg and 200 mg
Form covered here
Oral tablet
Oral tablet
Both contain the same mixture of R-modafinil and S-modafinil. Waklert and Artvigil belong to the separate armodafinil category. Our modafinil vs armodafinil comparison explains that molecular difference.[3]
Modalert vs Modvigil: Is Either Brand Better?
No direct published trial comparing Modalert with Modvigil was located in the research for this comparison. Both manufacturers list the same active ingredient and the same standard strengths. The available brand-specific evidence does not establish that either product improves focus more than the other.[1][2]
For the ingredient's clinical studies and uses, see the modafinil review. The accompanying video provides background on that shared ingredient.
Modalert vs Modvigil: Onset and Duration
A standard 200 mg tablet of either brand lists 200 mg of the same active ingredient. No product-specific comparative data were identified showing that Modalert consistently starts faster or lasts longer than Modvigil.[1][2]
A report about one person's experience cannot establish a predictable difference between these brands. When reviewing a change with a pharmacist, identify the exact tablet strength, formulation and dispensing source.
Modalert vs Modvigil: Formulation, Packaging and Price
The active ingredient is only part of a tablet. Fillers, binders, coatings and other inactive ingredients can vary between formulations. Someone with an excipient allergy needs the leaflet for the exact product dispensed, rather than an ingredient list copied from another modafinil brand.[4]
Compare prices for the same strength and number of tablets. A cheaper pack may simply contain fewer tablets. For a prescription filled locally, insurance coverage, dispensing fees and the available generic can also change the final cost.
Keep the dispensing label and original packaging when discussing a brand change with a pharmacist. They identify the exact product and batch involved. Appearance alone cannot establish tablet contents or authenticity.
Modalert and Modvigil: Tolerability When Switching
Modalert and Modvigil share the same active ingredient, so switching brands does not remove its adverse effects or interactions. Inactive ingredients can differ; check the exact product leaflet if an excipient allergy is relevant.[3][4]
See the modafinil review's safety section for the full risk profile. Stop treatment and seek prompt medical assessment for a new rash; breathing difficulty or swelling requires urgent help.[3]
Where to Buy Modalert or Modvigil
Availability depends on the country and its medicine approvals. In the United States, modafinil is a Schedule IV prescription medication. A licensed pharmacy can explain which approved products it can dispense against a valid prescription.[3]
For an online pharmacy, check its pharmacy-board license, prescription requirement and access to a pharmacist. These are the checks recommended by the FDA's BeSafeRx program.[5]
Eutropoflavin is 4'-dimethylamino-7,8-dihydroxyflavone, usually shortened to 4'-DMA-7,8-DHF. It is a synthetic flavone studied for neurotrophic signaling, cell survival, and behavior in mice. Early experiments reported TrkB-related activity; a later assessment obtained negative receptor-binding and functional results. [1][2][3]
What Is Eutropoflavin and Its Chemical Composition?
Eutropoflavin belongs to the flavone family. It has hydroxyl groups at positions 7 and 8 and a dimethylamino group at the 4' position. That additional dimethylamino group distinguishes it from 7,8-dihydroxyflavone. [1]
The 7 and 8 positions belong to the flavone A ring. Their neighboring hydroxyl groups form a catechol arrangement. The prime mark in 4' identifies a position on the separate phenyl B ring, where Eutropoflavin carries its dimethylamino substituent. The central oxygen-containing C ring completes the flavone framework.
These positions were central to the original medicinal-chemistry work. Researchers compared hydroxyl, methoxy, fluoro, and nitrogen-containing substitutions to see how changes in structure affected signaling. Eutropoflavin was identified as compound 6 in that derivative series. Searching the full chemical name or 4'-DMA-7,8-DHF retrieves the experimental literature more precisely than using the commercial name alone.[2]
Eutropoflavin: chemical structure and identifiers from PubChem. Figure by Nootropicology.
How Does Eutropoflavin Affect TrkB and BDNF Signaling?
TrkB is the receptor encoded by NTRK2. Its natural ligand, brain-derived neurotrophic factor (BDNF), participates in neuronal survival and synaptic signaling. Eutropoflavin research has examined small-molecule activity within this pathway. [3]
The original 2010 study identified 4'-DMA-7,8-DHF during a structure-activity investigation. The authors reported stronger or more sustained TrkB-related effects than with the parent compound in their experimental systems, alongside antiapoptotic findings. Chronic oral administration in mice was associated with dentate-gyrus neurogenesis and antidepressant-like behavioral effects. [2]
When BDNF activates TrkB, receptor-associated phosphorylation initiates intracellular signaling through pathways including PI3K-Akt, MAPK, and phospholipase C gamma. Phosphorylation means that a phosphate group has been added to a protein at a particular site. Researchers measured phosphorylated TrkB and downstream proteins to follow the response to the flavone derivatives.
In primary cortical neurons, the 2010 investigators observed Akt activation with both 7,8-DHF and Eutropoflavin at concentrations as low as 10 nM. Eutropoflavin produced a stronger response at 10 and 50 nM. At 100 nM and above, its measured Akt response was closer to that of the parent compound. The concentration-response relationship therefore varied across the tested range.[2]
Eutropoflavin Research: Why the TrkB Mechanism Is Disputed
Pankiewicz and colleagues assessed several proposed small-molecule TrkB agonists in 2021. Microscale thermophoresis found no detectable binding of 4'-DMA-7,8-DHF to the extracellular TrkB domain. The functional assays also returned negative results for the expected TrkB agonist activity. [3]
Original preclinical observations and a later independent assessment. Figure by Nootropicology.
Eutropoflavin Receptor Assays
The 2021 assessment examined binding, receptor activation, and dimerization, the pairing involved in receptor activation. It also tested whether the compounds enhanced BDNF's effects. For 4'-DMA-7,8-DHF, the tested systems showed neither the expected direct activation nor positive modulation of BDNF signaling. [3]
Assay
Measurement
2021 finding
Receptor binding
Microscale thermophoresis with the extracellular TrkB domain
No detectable binding.
Functional activity
Receptor activation and dimerization
Negative results for the expected activity.
BDNF modulation
Effect on the response to BDNF
No positive modulation in the tested systems.
The 2021 group used purified extracellular TrkB for its binding experiments. Microscale thermophoresis measures changes in the movement of fluorescently labeled molecules across a temperature gradient. Binding alters that movement, allowing an affinity estimate when a reproducible concentration-dependent signal is present. Eutropoflavin produced no detectable binding signal in this assessment.
The researchers then examined functional receptor responses and whether two TrkB molecules paired together, a process called dimerization. They also tested positive allosteric modulation: whether a candidate compound amplified the response to BDNF already present. Eutropoflavin returned negative results across these approaches. The same paper reported no cytoprotective activity for the reference compounds in its functional assessment.
The disagreement centers on the experimental results themselves. The 2010 study measured phosphorylation and protective responses in cortical neurons and mouse tissue; the 2021 work combined direct receptor-binding measurements with a separate panel of functional assays. Both studies identify the tested derivative as 4'-dimethylamino-7,8-dihydroxyflavone.[3]
Eutropoflavin Research Explained
Eutropoflavin Benefits: What Has Been Studied?
The published Eutropoflavin findings concern neurotrophic signaling, cell survival, and animal behavior. The PubMed research reviewed for this article consisted of preclinical studies.
Eutropoflavin Neurogenesis and Antidepressant-Like Effects
The original study reported neurogenesis in the mouse dentate gyrus, part of the hippocampal formation, following chronic oral administration. The same research program reported antiapoptotic activity and antidepressant-like behavioral effects. [2]
Adult male C57BL/6J mice received 5 mg/kg orally for 21 days in the original neurogenesis experiment. At the end of treatment, the investigators administered bromodeoxyuridine (BrdU), a marker incorporated during DNA synthesis. They examined the dentate gyrus 2 hours later and found more BrdU-labeled proliferating cells in treated animals than in vehicle-treated controls.
The behavioral experiment also followed 21 days of oral administration. Treated mice spent less time immobile in the forced-swim test. Researchers examined TrkB F616A knock-in mice to investigate the pathway further. This modified receptor can be selectively inhibited by the experimental compound 1NMPP1; applying that inhibitor eliminated the flavones' effect on immobility in those mice.[2]
Eutropoflavin Cell Survival Experiments
Cortical neurons were exposed to glutamate after pretreatment with the flavones. Investigators measured activated caspase-3, an enzyme involved in apoptosis. Both molecules reduced the glutamate-associated caspase-3 response at 50 nM and higher concentrations. At 10 nM, Eutropoflavin had a stronger inhibitory effect than 7,8-DHF.
A related mouse experiment used kainic acid to produce neural injury. The researchers tracked caspase-3 alongside TrkB phosphorylation after oral flavone administration. In the TrkB F616A animals, 1NMPP1 also abolished the protective response. These were the receptor-dependence experiments underlying the original paper's interpretation of Eutropoflavin's activity.[2]
The investigators followed the response at several points in the signaling chain. TrkB phosphorylation was measured alongside Akt and MAPK activation, and the cell-survival experiments used activated caspase-3 as their endpoint. In the chronic mouse experiments, hippocampal tissue staining and behavioral observations were collected after the same 21-day treatment period. The paper's proposed relationship between receptor signaling, cell proliferation, and behavior rests on this combination of measurements.[2]
Eutropoflavin vs. 7,8-DHF
Feature
7,8-DHF
Eutropoflavin
Chemical relationship
Parent flavone
4'-dimethylamino derivative
Substituents
Hydroxyl groups at positions 7 and 8
The same hydroxyl groups plus a 4'-dimethylamino group
Research context
Parent molecule in the structure-activity program
Derivative examined in the 2010 and 2021 studies
A 2012 optimization study investigated a further modified lead containing a pyrrolidinyl substituent and a fused imidazole system. The researchers reported improved laboratory ADMET characteristics and antidepressant-like effects in mice for that modified structure. [4]
The original comparison also examined the time course after a 1 mg/kg oral dose in mice. TrkB activation with 7,8-DHF peaked at approximately 1 to 2 hours. With Eutropoflavin, the reported peak occurred at 4 hours, followed by a partial decline over 8 to 16 hours. Downstream Akt and MAPK signals were also stronger and lasted longer with the dimethylamino derivative in that experiment.
Substitution experiments helped explain why the researchers retained the adjacent hydroxyl groups. Replacing the 7-hydroxyl group with methoxy modestly reduced the measured activity. Replacing both hydroxyl groups with methoxy substantially reduced it. The authors also tested changes to the central ring and reported weaker activity when its oxygen was replaced with an NH group.[2]
Eutropoflavin Dosage and Half-Life
Human therapeutic dosage and elimination half-life remain uncharacterized in the research reviewed here. The available exposure data come from cell, liver-preparation, and animal experiments.
The original experiments used different exposures for different questions. Cell-signaling assays tested nanomolar concentrations, the mouse time-course comparison used 1 mg/kg orally, and the chronic neurogenesis and behavioral experiments used 5 mg/kg orally for 21 days. These measurements appear together in the literature because the study combined molecular, tissue, and behavioral investigations.
The reported 4-hour peak concerned TrkB activation after oral administration. It describes the timing of a measured biological response. Plasma elimination half-life requires a separate concentration-time measurement of the compound itself. The 2021 microsomal experiments measured metabolic disappearance in liver-derived preparations and reported intrinsic clearance, another distinct measurement.[2]
Eutropoflavin Solubility, Permeability, and Metabolic Stability
The 2021 profiling found low solubility under the tested conditions, favorable membrane-permeability measurements, and substantial instability in human and mouse liver microsomes. Microsomes are liver-derived preparations used to study metabolism. [3]
At pH 7.4, the 2021 study classified Eutropoflavin's kinetic solubility as below 100 micromolar. The test measured how much compound remained dissolved after incubation in an aqueous buffer. Solubility addresses the amount available in solution, while the permeability experiments address movement across a membrane once the compound is dissolved.
Permeability exceeded the study's favorable threshold of 10-6 cm/s in both a parallel artificial membrane permeability assay (PAMPA) and the Caco-2 system. PAMPA uses an artificial membrane, while Caco-2 uses a cultured cell layer. Agreement between the two measurements gave Eutropoflavin a favorable permeability profile under those laboratory conditions.
Eutropoflavin Liver Metabolism
The metabolic result went in the opposite direction. Human and mouse liver microsomes degraded Eutropoflavin faster than the high-clearance reference compound verapamil. The researchers classified it as highly unstable in both species. Their analysis tracked the disappearance of the parent compound by liquid chromatography-mass spectrometry and expressed clearance relative to microsomal protein content.[3]
For the microsomal analysis, investigators incubated the compound with liver preparations and NADPH, a cofactor used by several metabolic enzymes. Samples were collected over the incubation period, and the remaining parent compound was measured against an internal analytical standard. Parallel human and mouse preparations allowed the same assay conditions to be compared between species.
The paper also tested chemical stability in buffer separately from enzymatic stability in microsomes. That distinction matters when reading an ADME table: low aqueous solubility, membrane transport, chemical breakdown, and liver-enzyme metabolism describe separate properties. Eutropoflavin combined favorable membrane transport with low solubility and rapid microsomal loss in this dataset.[3]
Eutropoflavin Side Effects and Safety
The reviewed literature provides preclinical activity and metabolic data. Human adverse-event rates remain uncharacterized. The Reddit discussion below includes reports of anxiety, impaired concentration, and sleep changes during use alongside other compounds.
Eutropoflavin User Experiences and Reddit Reviews
In a September 2026 r/Nootropics thread, the original poster described anxiety, reduced concentration, and later difficulty falling asleep while experimenting with Eutropoflavin alongside other compounds. Another commenter described calmer focus and less resistance to starting tasks. [5]
A commenter describes calmer focus with Eutropoflavin. The original poster in the same discussion reports a different experience. Read the original Reddit discussion.
The original poster also used piracetam, cytisine, and Noopept. Their later updates describe changing amounts, pauses in use, and changes in sleep and task switching.
Where to Buy Eutropoflavin: Swisschems Product Details
Swisschems lists 4'-DMA-7,8-DHF (Eutropoflavin) as 60 capsules containing 10 mg each, designated for research use.
Eutropoflavin Review Conclusion
Eutropoflavin's research record centers on a specific disagreement: the original study reported TrkB-related and behavioral effects, while the 2021 assessment found negative results in receptor-binding and functional assays. Its chemistry, animal findings, and laboratory metabolism data are better characterized than its effects in people.
Frequently Asked Questions About Eutropoflavin
The main Eutropoflavin questions concern its relationship to 7,8-DHF, TrkB activity, and cognitive research.
What Is Eutropoflavin Used For?
Eutropoflavin is used in experimental research on neurotrophic signaling, cell survival, and depression-related behavior. The original study reported increased neurogenesis and antidepressant-like effects in mice. Human treatment benefits have not been established.
How Does Eutropoflavin Differ From 7,8-DHF?
The difference between Eutropoflavin and 7,8-DHF is an additional dimethylamino group at the 4' position of the flavone structure. Eutropoflavin is therefore also called 4'-DMA-7,8-DHF. Its molecular formula is C17H15NO4, and its molecular weight is 297.30 g/mol.
Does Eutropoflavin Activate TrkB?
Whether Eutropoflavin directly activates TrkB remains disputed. The original study reported TrkB-related activity and effects in cells and mice. A 2021 assessment found no detectable receptor binding and negative results in the tested functional assays.
Do BDNF Supplements Such as Eutropoflavin Actually Work?
Eutropoflavin has not been shown to deliver the advertised benefits of a BDNF supplement in human trials. The original laboratory and animal study reported neurogenesis and behavioral changes in mice. Later experiments returned negative results for the expected direct TrkB activity.
Does Eutropoflavin Increase IQ?
Eutropoflavin has not been shown to increase human IQ. The studies reviewed here measured receptor activity, cellular markers, and mouse behavior. They did not measure changes in human intelligence-test scores.
NSI-189, also called amdiglurax and developed as ALTO-100, is an investigational compound studied for depression and cognitive symptoms. Its reputation as a neurogenesis enhancer comes largely from laboratory research. Human studies give a less straightforward picture: early exploratory findings were encouraging, but larger depression trials did not meet their primary efficacy endpoints. [1][2][3]
What Is NSI-189 and Its Chemical Composition?
NSI-189 is a synthetic small molecule containing benzylpiperazine and aminopyridine groups. Its free base and phosphate salt have separate PubChem records and different molecular weights. [4][5]
NSI-189 phosphate is a 1:1 salt. The free base has a molecular weight of 366.5 g/mol; the phosphate salt is 464.5 g/mol.
NSI-189: chemical structure and identifiers from PubChem. Figure by Nootropicology.
How Does NSI-189 Work?
NSI-189 was developed through research on neurogenesis, the formation of new neurons. Its clinical program subsequently examined depressive symptoms, cognitive performance, brain imaging, and pharmacokinetics. [1]
In a rat stroke study, investigators reported functional recovery alongside changes associated with neural repair. An Angelman syndrome mouse study examined synaptic plasticity and motor and cognitive outcomes. [6][7]
Neurogenesis concerns new neurons. Synaptic plasticity describes changes in communication between neurons. The NSI-189 research program has investigated both processes using cellular, tissue, and behavioral measurements.
The original screening program used human fetal hippocampal neural stem cells to identify molecules that increased neurogenesis. NSI-189 was then examined in healthy young adult mice, where investigators reported increased dentate-gyrus neurogenesis and hippocampal volume. This discovery strategy selected a cellular response rather than starting with inhibition of serotonin or norepinephrine reuptake, the mechanism targeted by several established antidepressant classes.
The hippocampus is involved in learning and memory, while its dentate gyrus contains neural precursor cells. The clinical program carried this anatomical focus into MRI measurements and cognitive testing. Those measurements address different features: MRI records regional volume, whereas computerized tasks record how accurately or quickly a participant responds.[2]
Does NSI-189 Increase Hippocampal Volume?
MRI measurements in the phase 1b trial showed no significant difference in hippocampal volume between the pooled NSI-189 and placebo groups at day 28 or day 84. The amygdala, used as a comparison region, showed similar trends. [1]
The imaging result is especially relevant because increased hippocampal volume was one of the preclinical observations that helped distinguish NSI-189 from other compounds in the screening program. In the human study, researchers pooled the active-treatment cohorts for the MRI comparison. The scans at the end of treatment and during follow-up therefore provide direct human anatomical results alongside the symptom questionnaires.[1]
NSI-189 Benefits and Clinical Trial Results
The clinical program includes a 24-patient phase 1b study, a 220-patient phase 2 study, and the later 301-participant ALTO-100 phase 2b trial. The early exploratory findings were followed by negative primary depression outcomes in the larger trials.
NSI-189 Phase 1b Trial: Early Exploratory Findings
Fava and colleagues enrolled 24 patients with major depressive disorder. Three cohorts received 40 mg once, twice, or three times daily, with 6 active-treatment patients and 2 placebo patients in each cohort. Treatment lasted 28 days, and follow-up continued to day 84. Exploratory SDQ and CPFQ scores favored NSI-189. [1]
A published correction replaced a duplicated efficacy figure and corrected an entry in a biomarker table. [8]
Participants stayed in an inpatient setting during the 28-day treatment period. Investigators assessed tolerability, collected pharmacokinetic samples, and repeatedly measured depressive and cognitive symptoms. Diagnosis and illness severity were confirmed through remote interviews. The three schedules corresponded to total daily exposures of 40, 80, and 120 mg.
Follow-up took place through outpatient visits after treatment ended. Improvements in the exploratory symptom measures persisted during that follow-up period. The study combined the six placebo recipients across cohorts when examining efficacy, giving the pooled comparison 18 active-treatment patients and 6 placebo patients. The larger outpatient trial subsequently tested two fixed daily regimens.[1]
NSI-189 Phase 2 Trial: The Primary Endpoint Was Not Met
The phase 2 study enrolled 220 patients and compared 40 mg/day and 80 mg/day with placebo over 12 weeks. The primary Montgomery-Asberg Depression Rating Scale (MADRS) comparison was negative for both regimens. Pooled differences were -1.8 points for 40 mg (p = 0.22) and -1.4 points for 80 mg (p = 0.34). [2]
Secondary patient-rated outcomes favored 40 mg/day on the Symptoms of Depression Questionnaire (SDQ) and Cognitive and Physical Functioning Questionnaire (CPFQ). The reported pooled differences were -8.2 points for SDQ (p = 0.04) and -1.9 points for CPFQ (p = 0.03). [2]
Researchers screened 353 people at 12 US sites before randomizing the 220 participants. Eligible patients were 18 to 60 years old, had a current major depressive episode lasting at least 8 weeks, and scored at least 20 on MADRS during screening and baseline assessments. The study investigated NSI-189 as monotherapy for major depressive disorder.
Its sequential-parallel comparison design divided the 12 weeks into two stages. Initially, 44 participants received 40 mg/day, 44 received 80 mg/day, and 132 received placebo. Placebo recipients who remained symptomatic after the first stage could enter a second randomization. Eligibility required less than a 50% MADRS reduction and a remaining score above 15.
This second stage reassigned eligible placebo nonresponders to either NSI-189 regimen or continued placebo. The primary analysis combined treatment estimates from the two stages. The clinician-rated Hamilton Depression Rating Scale, another depression endpoint, also showed no significant overall advantage. The favorable patient-reported findings were concentrated in the 40 mg group.[2]
NSI-189 Subgroup Analysis
Johe and colleagues reanalyzed the same 220-patient dataset by baseline depression severity. Their post-hoc analysis reported a more favorable response among moderately depressed patients. [9]
NSI-189 clinical studies and analyses. Figure by Nootropicology.
ALTO-100 Depression Trial Results
In October 2024, Alto Neuroscience reported topline results from a 301-participant phase 2b trial. The primary comparison focused on patients with a memory-based cognitive biomarker. Results were negative for the primary MADRS comparison and the prespecified key secondary analyses. [3]
Development continued in a separate bipolar depression program. In its second-quarter 2026 update, the company projected that trial's topline results for mid-2027. [10]
NSI-189 Depression and Cognitive Assessments
MADRS uses a clinician's assessment of depressive symptoms. SDQ and CPFQ record patients' experiences of symptoms and functioning. CogScreen and Cogstate assess performance on cognitive tasks.
Selected CogScreen measures favored the 40 mg group in the phase 2 study. Cogstate results showed no significant treatment advantage. [2]
Study
Participants and duration
Reported result
Phase 1b
24 patients; 28 treatment days; follow-up to day 84
Negative primary MADRS and key secondary results reported by the sponsor.
CogScreen included shifting-attention tasks, symbol-digit coding, delayed recall, and a previous-number task. Shifting-attention tests required participants to respond to changing rules, such as an arrow's color or direction. Symbol-digit coding assessed performance with paired symbols and numbers; delayed recall examined how well those associations were retained.
The investigators reported advantages on selected measures of mental flexibility, choice-reaction speed, and delayed recall of symbol-digit associations. They also examined responses following negative feedback. This is a more specific account of the cognitive findings than describing NSI-189 as improving memory across the board.
Cogstate used Detection, Identification, One Card Learning, and One Back tasks. The combined comparisons for these tasks were nonsignificant for both regimens. Within the patient-rated SDQ, favorable individual items included anxiety, mood responsiveness, decision-making, ability to work, and outlook on life. Removing the embedded CPFQ items from the SDQ calculation preserved the overall SDQ result.[2]
NSI-189 Memory Research
The human cognitive findings come from participants with depressive disorders. Researchers assessed both patient-reported cognitive difficulties and performance on standardized tasks.
Our Noopept review examines another compound studied for memory and neurotrophic effects.
In the stroke experiment, adult Sprague-Dawley rats began oral NSI-189 6 hours after middle cerebral artery occlusion. Treatment continued daily for 12 weeks, and improvements in motor and neurological deficits remained detectable up to 24 weeks after the stroke. Tissue analysis found increased microtubule-associated protein 2 (MAP2) staining, particularly in the hippocampus, consistent with greater neurite outgrowth.
The accompanying cell experiments used oxygen-glucose deprivation followed by reperfusion to model ischemic injury. NSI-189 reduced hippocampal cell death and increased the proliferation marker Ki67, MAP2, brain-derived neurotrophic factor, and stem cell factor. These experiments connect the behavioral findings with measured changes in injured neural tissue.[6]
The Angelman syndrome study examined a different experimental setting. NSI-189 increased theta-burst-stimulated long-term potentiation in hippocampal slices from both wild-type and Angelman-model mice. A short course of daily injections improved impaired motor and cognitive performance in the Angelman-model animals. The authors associated these effects with TrkB and Akt signaling.[7]
NSI-189 Dosage and Human Pharmacokinetics
In the phase 1b trial, plasma half-life ranged from 17.4 to 20.5 hours. Researchers measured concentrations using repeated blood samples. Overall exposure increased approximately in proportion to the administered dose. [1]
Half-life is the time taken for the measured concentration to fall by half. Under a simple elimination model, approximately 25% remains after 2 half-lives. Absorption and repeated administration also influence the concentration profile.
The trial reported exposure using area under the plasma concentration-time curve, or AUC. This measurement integrates the sampled concentrations over time. The nearly proportional increase across cohorts meant that higher administered regimens produced correspondingly higher overall measured exposure in that trial.
The study's once-daily, twice-daily, and three-times-daily schedules also made dosing frequency part of the pharmacokinetic comparison. Each administration contained 40 mg, while total daily amounts differed. The later phase 2 trial instead evaluated fixed daily totals of 40 and 80 mg over a longer treatment period. These are the regimens used in the clinical investigations, alongside the reported plasma elimination measurements.[1]
NSI-189 Side Effects and Safety
The 2024 ALTO-100 announcement listed headache, nausea, and abnormal dreams among the most common treatment-related adverse events, at similar rates to placebo. The sponsor reported no new safety signal. [3]
The earlier phase 2 trial reported no serious adverse events among participants randomized to NSI-189. During its first stage, neither active-treatment group had a discontinuation attributed to intolerance. During the second stage, intolerance led to one discontinuation in the 40 mg group, none in the 80 mg group, and one in the placebo group. Monitoring included laboratory tests, vital signs, physical examinations, and electrocardiograms.[2]
NSI-189 User Experiences and Reddit Reviews
A February 2026 discussion in r/Nootropics contains sharply different NSI-189 experiences. One commenter described better mental clarity and emotional regulation, but also mentioned using vortioxetine (Trintellix) and practicing meditation. Another later reported no noticeable effect. [11]
Contrasting NSI-189 reports: one commenter also used Trintellix and meditation; another later reported no effect. Read the original Reddit discussion.
Where to Buy NSI-189 Phosphate: Swisschems Product Details
Swisschems lists NSI-189 phosphate as 60 capsules containing 20 mg each. The listing designates it as a research product.
NSI-189 Review Conclusion
NSI-189's strongest early findings were changes in patient-reported symptoms. The larger depression studies returned negative primary outcomes, while selected secondary cognitive measures favored treatment. The ALTO-100 bipolar depression program continues that clinical investigation in a separate patient population.
Our nootropics guide compares other compounds studied for memory, attention, and mood.
Frequently Asked Questions About NSI-189
Common questions about NSI-189 concern its proposed mechanism, depression results, and reported side effects.
What Does NSI-189 Do?
NSI-189 is studied for effects on depressive symptoms, cognition, and neural plasticity. Laboratory and animal experiments have examined the formation of neurons and changes in communication between them. Human trials found some favorable secondary outcomes, but the larger depression trials missed their primary efficacy endpoints.
Is NSI-189 a Stimulant?
NSI-189 is an investigational antidepressant, rather than a conventional stimulant. Its development focused on neurogenesis and depressive and cognitive symptoms. The clinical trials assessed mood and cognition, not a stimulant indication such as promoting wakefulness.
Is NSI-189 Safe?
The long-term safety of NSI-189 is not established. The small phase 1b trial reported acceptable tolerability during its monitored treatment period. The 2024 ALTO-100 trial reported headache, nausea, and abnormal dreams at rates similar to placebo.
Is NSI-189 Neuroprotective?
NSI-189 has shown neuroprotective and neural-repair effects in animal research. A rat stroke study reported improved function alongside changes in neural tissue after treatment. A separate Angelman syndrome mouse study found improvements in synaptic plasticity and motor and cognitive performance.
What Are the Benefits of NSI-189 Phosphate?
The potential benefits of NSI-189 phosphate include improvements in selected depressive and cognitive symptoms reported in clinical trials. Early studies found favorable patient-rated outcomes, and the 220-patient phase 2 trial found improvements on some secondary measures. That phase 2 trial did not meet its primary depression endpoint.
