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Exploring Emerging Nootropics: Bromantane, Dihexa, Fladrafinil, Phenibut, Methylene Blue, Cerebrolysin, Pinealon, Semax, and Selank

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December 14, 2025
Exploring Emerging Nootropics: Bromantane, Dihexa, Fladrafinil, Phenibut, Methylene Blue, Cerebrolysin, Pinealon, Semax, and Selank

Exploring Emerging Nootropics: Bromantane, Dihexa, Fladrafinil, Phenibut, and Methylene Blue, Cerebrolysin, Pinealon, Semax, and Selank

December 23, 2025

Nootropics, commonly known as cognitive enhancers or “smart drugs,” are substances intended to improve mental functions such as memory, focus, motivation, and resilience to stress. While established compounds like piracetam are well-studied, emerging nootropics including Bromantane, Dihexa, Fladrafinil (CRL-40,941), Phenibut, Methylene Blue, Cerebrolysin, Pinealon, Semax, and Selank have drawn interest for their unique profiles, often rooted in Russian research traditions.

Methylene Blue qualifies as a nootropic candidate via mitochondrial enhancement, while Cerebrolysin, Pinealon, Semax, and Selank represent peptide-based neurotrophic and regulatory agents with strong preclinical and clinical data from Russia.[1] This article reviews each compound’s mechanisms and research-supported effects, primarily from preclinical and limited clinical data. Evidence is often animal-based or from Russian sources; human trials are sparse. These substances are experimental and carry risks.

Compound-by-Compound Analysis

Bromantane

  • Adamantane derivative developed in Russia as an actoprotector for enhancing performance under stress
  • Upregulates dopamine synthesis via increased expression of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD)[2][3][4]
  • Psychostimulant effects without typical amphetamine-like hyperactivity or dependence risk[5][6]
  • Improves physical work capacity, reduces fatigue, and protects mitochondria under extreme loads[7][8]
  • Enhances memory, vigilance (EEG changes), operant behavior, and shows anxiolytic-like effects[9]
  • Evidence primarily from Russian preclinical and human studies for asthenia and fatigue[10]

Dihexa

  • Orally active, blood-brain barrier-permeable angiotensin IV analog
  • Potent agonist of the HGF/c-Met system, promoting synaptogenesis and dendritic arborization via PI3K/AKT pathways[11][12][13]
  • Rescues cognitive deficits and restores spatial memory in Alzheimer’s models (e.g., Morris water maze)[14][15]
  • Increases synaptic markers (synaptophysin) and reduces neuroinflammation[16]
  • Promotes neurogenesis and spine density in impaired models; minimal effects in healthy animals[17]
  • Research limited to preclinical studies; no human trials reported[18]

Fladrafinil (CRL-40,941)

  • Fluorinated analog of adrafinil (prodrug to modafinil); classified as a eugeroic (wakefulness-promoter)
  • Likely inhibits dopamine reuptake and modulates histamine, similar to modafinil[19][20]
  • Shows anti-aggressive effects in animal models (distinct from adrafinil)[21]
  • Potential wakefulness and cognitive benefits extrapolated from modafinil family[22]
  • Scientific literature extremely limited; primarily analytical/chemical studies, no dedicated efficacy trials[23]

Phenibut

  • β-Phenyl derivative of GABA; primarily GABAB receptor agonist with some GABAA activity[24][25]
  • Weakly inhibits voltage-gated calcium channels; may stimulate dopamine[26]
  • Anxiolytic and tranquilizing effects; used clinically in Russia for anxiety, insomnia, and tension[27][28]
  • Secondary nootropic-like effects in asthenia and vestibular disorders[29]
  • High risk of tolerance, dependence, and severe withdrawal (delirium, seizures)[30][31][32][33]

Methylene Blue

  • Thiazine dye acting as mitochondrial electron cycler; enhances cytochrome oxidase and respiration[34]
  • At low doses reduces oxidative stress and improves energy metabolism[35]
  • Enhances memory retention (fear extinction, spatial tasks) in healthy and impaired models[36][37]
  • Attenuates deficits in hypoperfusion, TBI, and Alzheimer’s models; reduces Aβ and tau pathology[38][39]
  • Neuroprotective; preliminary human studies show improved attention and short-term memory[40][41]

Cerebrolysin

  • Porcine brain-derived peptide mixture with neurotrophic properties similar to endogenous growth factors
  • Multimodal: neurotrophic stimulation, neuroprotection, anti-apoptosis, and synaptic plasticity enhancement[42][43]
  • Improves cognitive function in mild-to-moderate Alzheimer’s (global impression, memory) and vascular dementia; enhances recovery in TBI and stroke[44][45][46][47]
  • Promotes neurogenesis and reduces amyloid/tau pathology in models[48]
  • Evidence from multiple RCTs and meta-analyses (mostly mild-moderate AD/TBI); approved in some countries for neurological conditions[49][50][51]

Pinealon

  • Synthetic tripeptide (Glu-Asp-Arg); bioregulator derived from pineal gland/Cortexin fractions
  • Modulates gene expression, reduces oxidative stress/apoptosis, and supports neuronal metabolism/mitochondrial function[52][53]
  • Improves memory, learning, and cognitive resilience in aging/stress models; neuroprotective against hypoxia and age-related decline[54][55][56]
  • Preclinical/animal data dominant; limited human studies, often in combination therapies[57][58]

Semax

  • Synthetic ACTH(4-10) analog (Met-Glu-His-Phe-Pro-Gly-Pro); intranasal nootropic
  • Increases BDNF/NGF, modulates dopamine/serotonin, provides neuroprotection against hypoxia/glutamate toxicity[59][60][61]
  • Enhances memory, attention, learning under stress; improves stroke/TBI recovery and cognitive performance[62][63][64]
  • Clinical use in Russia; strong preclinical and some human data for nootropic/neuroprotective effects[65][66][67]

Selank

  • Synthetic tuftsin analog heptapeptide; intranasal anxiolytic with nootropic properties
  • Allosteric modulator of GABAA receptors; modulates enkephalins, serotonin, and immune/inflammatory genes[68][69][70]
  • Pronounced anxiolytic effects without sedation/dependence; mild nootropic benefits (memory, attention)[71][72][73]
  • Clinical use in Russia for anxiety disorders; good tolerability and lasting effects post-treatment[74][75][76]

Master Comparison Table

Compound Primary Mechanism Key Research Benefits (Research) Evidence Level Risks/Notes
Bromantane Dopamine synthesis upregulation Fatigue reduction, stamina, mild stimulation, memory optimization Animal + Russian human Low addiction risk
Dihexa HGF/c-Met agonism; synaptogenesis Memory rescue in impairment models; anti-inflammatory Preclinical only No human data
Fladrafinil Dopamine reuptake inhibition Wakefulness, anti-aggression Very limited Unknown long-term
Phenibut GABAB agonism Anxiety reduction, sedation Animal + Russian clinical High dependence/withdrawal
Methylene Blue Mitochondrial enhancement Memory enhancement, neuroprotection Animal + emerging human Safe at low doses
Cerebrolysin Neurotrophic/neuroprotective peptides Cognitive improvement in AD/TBI/stroke Multiple RCTs/meta-analyses Injection-related; generally safe
Pinealon Gene expression modulation; antioxidant Neuroprotection, memory in aging models Preclinical dominant Limited data
Semax BDNF/NGF upregulation; neuromodulation Memory, focus, stroke/TBI recovery Preclinical + Russian clinical Low; intranasal well-tolerated
Selank GABAA allosteric modulation Anxiolytic, mild nootropic Clinical in Russia Minimal; no dependence

Scroll left and right to see all table columns and rows

Potential Synergistic Uses

  • No direct studies on combinations of these specific compounds. Synergies are hypothetical/anecdotal from user communities:
  • Bromantane + Methylene Blue: Dopamine upregulation + mitochondrial energy could enhance motivation and sustained focus without crash.
  • Dihexa + Methylene Blue: Synaptogenesis + neuroprotection for long-term cognitive repair in aging/impairment.
  • Fladrafinil + Phenibut: Wakefulness + anxiety reduction (similar to modafinil + GABAergics stacks).
  • Semax + Selank: Common Russian stack for balanced cognition (focus) + anxiety reduction.
  • Cerebrolysin + Semax/Selank: Neurotrophic support + targeted modulation for recovery.
  • Bromantane/Methylene Blue + Pinealon: Energy/mitochondrial + gene-level neuroprotection.
  • Avoid Phenibut with others due to GABA risks amplifying sedation/dependence. Combinations increase unknown interactions/risks. Consult professionals; these are experimental.

References

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All information presented for research and educational purposes only. Consult a healthcare professional before use. These are not FDA-approved for cognitive enhancement in the US.

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