NSI-189 PHOSPHATE

APPLICATIONS AND BENEFITS:

1. Depression Management: NSI-189 has demonstrated the ability to attenuate symptoms associated with major depressive disorder through specific neurotransmitter modulation.

2. Neuroplasticity Enhancement: The compound promotes neuronal plasticity, facilitating adaptability within neural networks and synaptic connections.

3. Cognitive Clarity Enhancement: NSI-189 has been found to reduce mental confusion, likely through its impact on specific neural pathways and neurotransmitter activity.

4. Age-Related Cognitive Decline Mitigation: Research indicates potential efficacy in counteracting cognitive decline associated with aging processes.

5. Diabetic Neuropathy Symptom Reduction: NSI-189 has exhibited therapeutic potential in managing neuropathic symptoms in diabetic patients.

6. Ischemic Stroke Recovery Aid: The compound may expedite recovery following ischemic stroke events through neuroprotective mechanisms.

7. Angelman Syndrome Motor Recovery Assistance: Preliminary studies suggest NSI-189 could facilitate motor recovery in Angelman Syndrome cases.

8. Neuroprotection against Injury or Irradiation: The compound offers protection against brain injury and irradiation-induced damage, likely through antioxidant and anti-apoptotic pathways.

9. Alzheimer's Disease Memory Enhancement: NSI-189 has shown promise in expanding memory capabilities within the context of Alzheimer's disease.

10. Restoration of Brain Cells: Evidence suggests significant improvements in restoring brain cells, potentially through mechanisms involving neural growth factors.

NSI-189 represents a significant advancement in the field of research, exhibiting a diverse range of therapeutic benefits. The compound's intricate interactions with neural pathways and biochemical mechanisms warrant further investigation to elucidate its potential applications and long-term effects fully. Its current applications underscore the scientific and clinical interest in NSI-189 as a promising candidate for treating various neurological and psychiatric conditions.

NSI-189 REVIEW: A DETAILED ANALYSIS

Introduction to NSI-189 and Nootropic Chemicals: 

NSI-189 is classified within the diverse family of nootropic agents which enhance cognitive faculties. Initially, the term 'nootropics' referred to specific chemicals adhering to strict criteria, but it has since broadened to encompass any natural or synthetic substances that positively impact cognitive abilities.

Chemical Structure and Neurogenic Properties: 

NSI-189, a benzylpiperazine-aminopyridine derivative, is an experimental neurogenic compound. It is being investigated for therapeutic applications in conditions such as Major Depressive Disorder (MDD), stroke, cognitive impairment, traumatic brain injury, and age-related neurodegeneration. NSI-189 facilitates neurogenesis in the hippocampus and expedites the development of neural stem cells.

Mechanisms of Action and Effects: 

The compound's novel neurogenic properties appear to be driven by multi-factorial mechanisms, resulting in antidepressant qualities, mental confusion reduction, synaptic plasticity improvement, and neurotrophic activities.

1. Synaptic Plasticity: Two general forms, intrinsic and extrinsic, represent synaptic plasticity. Innate mechanisms relate to activity-driven changes in synapse strength, while extrinsic mechanisms are associated with changes in synapse strength due to activity in alternate pathways.
2. Antidepressant Activity: The antidepressant efficacy of NSI-189 is monoamine-independent, with clinical trials conducted in patients with recurrent MDD.
3. Beneficial Applications in MDD: MDD, characterized by pervasive low mood episodes, is a significant health concern and a leading cause of disability within the U.S. population aged 15 to 44.
4. Discovery and Development: Systematic chemical library screening led to NSI-189's discovery, utilizing in vitro models of human hippocampal neurogenesis. Its unique mode of action is independent of serotonin or norepinephrine reuptake inhibition pathways.

Effects on the Brain:

NSI-189's distinctive impact on the hippocampal region differentiates it from other antidepressants. It specifically targets, and screens compounds responsible for hippocampal increases in rodent models. The hippocampus plays a critical role in memory consolidation and spatial navigation.

Dosage and Clinical Trials: 

A randomized trial involving 220 human subjects investigated dosages of NSI-189 at 40mg and 80mg daily, or placebo, for 12 weeks. The primary outcome was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS).

Safety Profile: 

The compound exhibited favorable tolerability in clinical trials, consistent with Phase 1b study results. Studies on rodents have shown enhanced brain and motor functions post-stroke, and NSI-189 has been observed to reverse cell death caused by oxygen deprivation, with effects lasting 24 weeks.

Chemical Information:

• IUPAC Name: (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone
• CAS Number: 1270138-40-3
• Molecular Formula: C22H33N4O5P
• Molar Mass: 366.5 g/mol