NSI-189 60x30mg

                                         NOT FOR HUMAN CONSUMPTION

NSI-189 is an experimental compound originally developed by Neuralstem, Inc. (now Palisade Bio). Classified as a novel neurogenic and neuroprotective agent, NSI-189 gained attention due to its unique mechanism of action, promoting neurogenesis (the growth of new neurons) in the hippocampal region of the brain, an area critical for memory, mood, and cognition. Initially studied for major depressive disorder (MDD) and cognitive decline, NSI-189 remains under investigation and is currently not approved by the U.S. FDA or any major regulatory agency for medical use.

Chemical and Pharmaceutical Background

• Compound Name: NSI-189

• Classification: Novel neurogenic compound

• Chemical Structure: Benzylpiperazine-aminopyridine derivative

• Developer: Neuralstem, Inc. (Palisade Bio)

• Administration Route: Oral (capsules/powder)

Mechanism of Action

NSI-189’s precise mechanism remains partially understood but is notable for its potentially unique pathway:

1. Hippocampal Neurogenesis Stimulation

• NSI-189 stimulates the proliferation and differentiation of neural stem cells, increasing neurogenesis specifically within the hippocampus.

• Increased hippocampal volume could theoretically enhance memory, mood regulation, and cognitive function.

2. Neurotrophic Factor Regulation

• Studies indicate that NSI-189 may enhance levels of brain-derived neurotrophic factor (BDNF), essential for neuronal growth, plasticity, and survival.

3. Synaptic Plasticity Enhancement

• May enhance synapse formation, strength, and plasticity, facilitating improved cognitive function and learning abilities.

4. Reduction of Neuroinflammation

• Early findings suggest anti-inflammatory properties within neural tissues, potentially beneficial in neurological diseases and mood disorders associated with inflammation.

Potential Therapeutic Applications

1. Major Depressive Disorder (MDD)

• Clinical studies primarily investigated NSI-189 as a novel antidepressant due to its hippocampal neurogenic properties, potentially offering an innovative alternative mechanism compared to current antidepressants.

2. Cognitive Enhancement

• Interest in nootropic communities is driven by the potential cognitive benefits from enhanced neurogenesis and hippocampal plasticity.

3. Neurodegenerative Diseases

• Preliminary interest in exploring NSI-189’s potential benefit in Alzheimer’s disease, Parkinson’s disease, stroke recovery, and traumatic brain injury, though clinical trials for these uses remain limited.

4. Post-Traumatic Stress Disorder (PTSD)

• Potential interest due to hippocampal atrophy associated with PTSD; the compound’s neurogenic properties could theoretically address hippocampal volume reduction observed in PTSD patients.

Clinical Research Findings

Clinical Trials Overview

NSI-189 has completed initial phases of clinical testing, notably:

• Phase Ia/b (Healthy volunteers and MDD patients):

  • Showed promising tolerability, safety, and signs of improved mood and cognitive measures.

• Phase II clinical trial (MDD patients):

  • Mixed results: primary endpoints not conclusively met, although secondary endpoints indicated improvements in depressive symptoms and cognition in subsets of participants.

  • Some participants reported subjective improvements in cognition, mood stability, and overall quality of life.

Summary of Clinical Evidence

• Positive Aspects:

  • Reported mood improvements, reduced depressive symptoms.

  • Possible cognitive enhancements (memory, concentration, clarity).

  • Generally well-tolerated with limited adverse effects.

• Limitations:

  • Small sample sizes and short durations limit the reliability of results.

  • Phase II results were mixed, highlighting the need for additional larger-scale trials.

  • Insufficient data for definitive conclusions regarding efficacy.

Dosing and Administration (Experimental Context)

While NSI-189 lacks officially established dosing guidelines, clinical trials and anecdotal community experimentation often reference these regimens:

• Common Experimental Dosage:

  • Typically 40–80 mg per day, orally, divided into one or two doses.

  • Clinical studies used doses ranging from 40 mg to 80 mg daily over 4–12 weeks.

• Cycle Duration:

  • Experimental cycles commonly range from 4–8 weeks, followed by breaks to monitor cognitive changes and side effects.

• Important Considerations:

  • Users often suggest starting at the lowest effective dose, increasing gradually if necessary.

  • Regular monitoring of cognitive function and mood is encouraged.

Safety Profile and Side Effects

Clinical Safety Data

Based on published trial data, NSI-189 is generally regarded as having a favorable short-term safety profile. However, data on long-term safety are limited.

Reported Adverse Effects (Clinical Trials & Anecdotal Reports):

• Mild to moderate headaches

• Fatigue or sleepiness

• Dizziness

• Gastrointestinal discomfort or nausea

• Mild anxiety or restlessness (occasional reports)

Long-Term Safety Concerns

• The long-term safety profile remains unclear due to insufficient extended studies.

• No significant severe adverse effects were noted in short-duration clinical trials, but comprehensive long-term research remains necessary.

Comparison to Other Treatments

• NSI-189 vs. Traditional Antidepressants:

  • Mechanism differs significantly from SSRIs, SNRIs, or other common antidepressants, potentially addressing treatment-resistant depression through novel neurogenic pathways.

  • Possibly fewer sexual or emotional blunting side effects compared to SSRIs.

• NSI-189 vs. Other Nootropics (e.g., racetams, ampakines):

  • Uniquely promotes structural neurogenesis, whereas other nootropics usually enhance neurotransmitter signaling or cerebral blood flow without necessarily causing neuronal growth.

  • Possibly complementary to traditional nootropics rather than directly comparable.

Legal Status and Availability

• NSI-189 is not approved by FDA or other regulatory agencies for clinical treatment.

• It is available primarily through research chemical suppliers for "research purposes only" and is not intended or legally marketed for human consumption.

• Potential users should thoroughly verify local laws and regulations before acquisition or experimentation.

Current Limitations and Challenges

• Lack of Large-Scale Human Data:

  • The compound remains experimental, and current data are insufficient for definitive clinical recommendations.

• Unknown Long-Term Effects:

  • Risks of chronic administration remain largely unstudied.

• Regulatory and Quality Assurance:

  • Research chemical markets lack standardized regulation, creating potential risks around product purity, authenticity, and safety.

References 

1. Fava, M., et al. (2016). "NSI-189, a neurogenic compound, in major depressive disorder: results from a randomized, placebo-controlled, double-blind, Phase 1b trial." Molecular Psychiatry, 21(10), 1372–1380.

2. McIntyre, R. S., et al. (2019). "Neurogenic antidepressants: NSI-189 and implications for major depressive disorder treatment strategies." Expert Opinion on Investigational Drugs, 28(3), 249–255.

3. Hanson, N. D., et al. (2019). "Neurogenic compound NSI-189 affects synaptic plasticity and hippocampal neurogenesis." Neuropsychopharmacology, 44(4), 669–679.