Nootropic Compounds

Potent psychoactive and neuroactive chemicals that play key roles in modulating receptor sites, synaptic enzymes, membrane structures, cerebral perfusion, biogenic processes, neuroendocrine regulation and more.


Nootropic Compounds - Noopeptic

Noopept

Overview:
Noopept is a potent receptor site modulator and nootropic. Studies indicate its ability to increase memory and attention span, reduce anxiety and depressive symptoms, and exhibit neuroprotective qualities.

Scientific Name:
N-phenylacetyl-L-prolylglycine ethyl ester

Mechanisms:

  • Racetam like properties (NMDA receptor modulator) and Ampakine like properties (AMPA glutamate receptor modulator)[1]
  • In the vicinity of 1,000 times the potency of piracetam[2]
  • Upregulates neurotrophin factors NGF and BDNF involved in neurogenesis and long term memory[3]
  • Acetylcholine and glutamate sensitizing effect[4,5]
  • Modulates EEG patterns in ways considered positive for calm alertness[1]
  • Neuroprotective effects from oxidative stress and glutamate excitotoxicity[6]
  • Anxiolytic effect – may be due to hippocampal regulation[7]
  • Cycloprolylglycine precursor – an endogenous anxiolytic neuropeptide[8]
References

[1] Vorobyov V, et al (2011). Effects of nootropics on the EEG in conscious rats and their modification by glutamatergic inhibitors. Brain Res Bull, 85(3-4):123-32. doi: 10.1016/j.brainresbull.2011.02.011
[2] Solntseva EI et al (1997). The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels. Gen Pharmacol, 29(1):85-9. doi: 10.1016/S0306-3623(96)00529-0
[3] Ostrovskaya RU et al (2008). Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Bull Exp Biol Med, 146(3):334-7. doi: 10.1007/s10517-008-0297
[4] Firstova IuIu, et al (2011). Studying specific effects of nootropic drugs on glutamate receptors in the rat brain. Eksp Klin Farmakol, 74(1):6-10. PMID: 21476267
[5] Ostrovskaia RU, et al (2001). Behavioral and electrophysiological analysis of the choline-positive effect of nootropic dipeptide acylproline (GVS-111). Eksp Klin Farmakol, 64(2):11-4. PMID: 11548439
[6] Andreeva NA, et al (2000). Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress. Bull Exp Biol Med, 130(10):969-72. doi: 10.1023/2FA.3A1002828707337
[7] Kondratenko RV, et al (2010). Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells. Neurosci Lett, 476(2):70-3. doi: 10.1016/j.neulet.2010.04.005
[8] Gudasheva TA et al (1997). The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine. Eur J Drug Metab Pharmacokinet, 22(3):245-52. doi: 10.1007/2FBF03189814

Nootropic Compounds - Phenylethylamine

Phenylethylamine

Overview:
PEA is an endogenous neurotransmitter and neuroregulator that plays a key role in mood and cognition, popularly known as the “love drug”. It is Associated with states of heightened arousal, euphoria, and excitation, as well as increased attention and concentration.

Scientific Name:
Phenylethylamine, (PEA)

Mechanisms:

  • Stimulates dopamine, norepinephrine, and acetylcholine levels[1]
  • Modulates receptor sensitivity and reuptake processes[1]
  • Synthesized in the body from the amino acid phenylalanine[2]
  • Psychoactive ingredient in chocolate and blue green algae[3,4]
  • Synergistic with MAO-B inhibitors like Hordenine[5]
  • Phenylethylamines are a category of empathogens and entheogens derived from PEA and that act largely on its receptor sites[1]
References

[1] Xie Z1 & Miller GM (2008). Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther, 325(2):617-28. doi: 10.1124/jpet.107.134247
[2] Berry MD (2004). Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem, 90(2):257-71. doi: 10.1111/j.1471-4159.2004.02501.x
[3] Granvogl M, et al (2006). Formation of amines and aldehydes from parent amino acids during thermal processing of cocoa and model systems: new insights into pathways of the strecker reaction. J Agric Food Chem, 54(5):1730-9. doi: 10.1021/jf0525939
[4] Güven KC et al (2010). Alkaloids in marine algae. Mar Drugs, 8(2):269-84. doi: 10.3390/md8020269
[5] Cashin CH (1972). Effect of sympathomimetic drugs in eliciting hypertensive responses to reserpine in the rat, after pretreatment with monoamineoxidase inhibitors. Br J Pharmacol. 1972 Feb;44(2):203-9. doi: 10.1111/j.1476-5381.1972.tb07256.x

Nootropic Compounds - Hordenine HCI

Hordenine HCI

Overview:
Hordenine is a natural MAO-B inhibitor found in barley grass. It is a potentiator of PEA and all neurotransmitters that are degraded by MAO-B. It is often taken for increased energy, alertness, concentration, and metabolism

Scientific Name:
N,N-dimethyltyramine extracted from Hordeum vulgare

Mechanisms:

  • Natural and relatively selective MAO-B inhibitor[1]
  • Synergistic with PEA, Catecholamines, and Caffeine
  • Amine with adrenergic properties[2]
  • Analogue of the endogenous neurotransmitter tyramine[2]
References

[1] Barwell CJ et al (1989). Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat. J Pharm Pharmacol, 41(6):421-3. doi: 10.1111/j.2042-7158.1989.tb06492.x
[2] Hapke HJ & Strathmann W (1995). Pharmacological effects of hordenine. Dtsch Tierarztl Wochenschr, 102(6):228-32. PMID: 8582256

Nootropic Compounds - Phosphatidylserine

Phosphatidylserine

Overview:
PS is a naturally occurring aminophospholipid found in high concentrations in the brain. Studies indicate its ability to reduce stress, fatigue, attention deficit and forgetfulness, and to increase mental processing speed and accuracy, attention and working memory.

Scientific Name:
Phosphatidylserine, (PS)

Mechanisms:

  • Essential component in cell lipid membranes
  • Signaling agent for apoptosis[1]
  • Increases aerobic capacity, possibly through hormone regulation[2,3]
  • Can be converted to other phospholipids including phosphatidylcholine
  • Involved in neurotransmitter modulation and intercellular communication[4]
  • Enhances brain glucose metabolism[5]
  • Global enhancement of mental function shown on EEG[6]
  • Increases NGF activity[7]
References

[1] Lee SH, et al (2013). Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking between plasma membrane and cytoplasm. Cell Death Differ, 20(1):64-76. doi: 10.1038/cdd.2012.93
[2] Kingsley MI, et al (2006). Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc, 38(1):64-71. PMID: 16394955
[3] Monteleone P, et al (1990). Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology, 52(3):243-8. doi: 10.1159/000125593
[4] Pedata F, et al (1985). Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol Aging, 6(4):337-9. doi: 10.1016/0197-4580(85)90013-2
[5] Klinkhammer P, et al (1990). Effect of Phosphatidylserine on Cerebral Glucose Metabolism in Alzheimer’s Disease. Dement Geriatr Cogn Disord, 1:197–201. doi: 10.1159/000107142
[6] Heiss WD, et al (1994). Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer’s disease. A neuropsychological, EEG, and PET investigation. Dement Geriatr Cogn Disord, 5(2):88-98. doi: 10.1159/000106702
[7] De Simone R, et al (2003). Apoptotic PC12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells. J Neuropathol Exp Neurol, 62(2):208-16. doi: 10.1093/jnen/62.2.208

Nootropic Compounds - Vinpocetine

Vinpocetine

Overview:
Vinpocetine is a vasoactive alkaloid derived from Periwinkle with neuroprotective and nootropic actions. Studies indicate that vinpocetine can benefit attention and memory, decrease fatigue and increase alertness.

Scientific Name:
Ethyl apovincaminate

Mechanisms:

  • Neuroprotective against a wide array of neurotoxic chemicals – through inhibition of voltage-gated sodium channels and reduction of calcium-influx into neuronal cells[1]
  • Anti-inflammatory activity – reduces TNFα-induced expression of pro-inflammatory molecules[2]
  • Cerebral vasodilation through phosphodiesterase (PDE) type-1 inhibition – increased blood flow in the brain[3]
  • Improved brain metabolism due to increased glucose availability – leading to increased neuronal ATP
  • Upregulates acetylcholine, noradrenaline, serotonin, and dopamine receptors[4,5]
  • Cerebral antioxidant[6]
References

[1] Bönöczk P, et al (2000). Role of sodium channel inhibition in neuroprotection: effect of vinpocetine. Brain Res Bull, 53(3):245-54. doi: 10.1016/S0361-9230(00)00354-3
[2] Wang H, et al (2014). Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury. Neurosci Lett, 566:247-51. doi: 10.1016/j.neulet.2014.02.045
[3] Hagiwara M, et al (1984). Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle. Biochem Pharmacol, 33(3):453-7. doi: 10.1016/0006-2952(84)90240-5
[4] Gaál L & Molnár P (1990). Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus. Eur J Pharmacol, 187(3):537-9. doi: 10.1016/0014-2999(90)90383-H
[5] Herrera-Mundo N & Sitges M (2013). Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings. J Neurochem. 124(2):233-40. doi: 10.1111/jnc.12082
[6] Solanki P, et al (2011). Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture. Food Chem Toxicol, 49(4):917-22. doi: 10.1016/j.fct.2010.12.015

Nootropic Compounds - Huperzine-A

Huperzine A

Overview:
Huperzine A is a potent natural synaptic enzyme modulator. Studies indicate its ability to support learning, memory, neuroplasticity, and executive function.

Scientific Name:
Huperzine A extracted  from Huperzia serrata

  • Acetylcholinesterase inhibitor[1]
  • NMDA receptor antagonist[1]
  • Neuroprotective against hydrogen peroxide damage, glutamate excitotoxicity, and beta amyloid pigmentation[1]
  • Neurogenic through increased proliferation of hippocampal neural stem cells and NGF stimulation[2]
  • Upregulates REM sleep (many report increased lucid dreaming)
  • Supports memory consolidation and neuroplasticity[1]
  • Synergistic with cholinomimetics and cholinosensitizers
References

[1] Wang R, et al (2006). Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin, 27(1):1-26. doi: 10.1111/j.1745-7254.2006.00255.x
[2] Ma T, et al (2013). Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res, 1506:35-43. doi: 10.1016/j.brainres.2013.02.026

Nootropic Compounds - Theobromine

Theobromine

Overview:
Theobromine is a methylxanthine related to caffeine extracted from cocoa (Theobroma Cacao) beans. Studies show that theobromine increases alertness, attention, and executive function.

Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao

Mechanisms:

  • A xanthine related to and synergistic with caffeine as a CNS stimulant, with slower onset and longer duration than caffeine[1]
  • Adenosine receptor antagonist (lower affinity than caffeine)[1]
  • Affects neurotransmitters modulated by Adenosine – Noradrenaline, Dopamine, Serotonin, Acetylcholine, Glutamate, and GABA[3]
  • PDE inhibitor, increases intracellular cAMP[2]
  • Increases motor activity[3]
  • Increases information processing rate[3]
  • Increases cerebral metabolism and vasodilation[3]
  • The natural stimulant found in Chocolate (Theobroma) contributing to Cacao’s effect on mood (along with phenylethylamine)[1]
References

[1] Franco R, et al (2013). Health benefits of methylxanthines in cacao and chocolate. Nutrients, 18;5(10):4159-73. doi: 10.3390/nu5104159
[2] Essayan DM (1999). Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol, 57(9):965-73. doi: 10.1016/S0006-2952(98)00331-1
[3] Burnstock G (2013). Introduction to purinergic signalling in the brain. Adv Exp Med Biol, 986:1-12. doi: 10.1007/978-94-007-4719-7_1

Nootropic Compounds - Pure Energy

Pure Energy (Pterostilbene bound to Caffeine)

PureEnergy®

Caffeine-pTeroPure® Co-crystal

Overview:
PureEnergy is a patented compound binding caffeine with the potent antioxidant pterostilbene. Binding caffeine with pterostilbene significantly slows the absorption rate of caffeine lengthening its half life and delivering up to 30% more total effect while reducing typical caffeine crash symptoms.

Caffeine

Overview:
Caffeine is a methylxanthine found in coffee beans, cocoa beans and in tea. Research shows that caffeine is a brain stimulant that increases alertness, wakefulness, attention, working memory, and motor activity.

Scientific Name:
1,3,7-trimethylxanthine

Mechanisms:

  • Adenosine receptor antagonist[1]
  • Affects neurotransmitters modulated by Adenosine: Noradrenaline, Dopamine, Serotonin, Acetylcholine, Glutamate, and GABA[1]
  • Phosphodiesterase inhibitor[2]
  • Increases motor activity through inhibition of acetylcholinesterase
  • Increases cortical activation in the brain[1]
  • Increases information processing rate and concentration[1]
  • Increases cerebral metabolism[1]

More Info:

References

[1] Burnstock G (2013). Introduction to purinergic signalling in the brain. Adv Exp Med Biol, 986:1-12. doi: 10.1007/978-94-007-4719-7_1
[2] Essayan DM (1999). Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol, 57(9):965-73. doi: 10.1016/S0006-2952(98)00331-1

Pterostilbene as pTeroPure

Overview:
Pterostilbene is a powerful cerebral antioxidant and neuroprotectant found naturally in blueberries. Research indicates that pterostilbene may reduce age-related cognitive decline, improving memory, concentration, and learning.

Scientific Name:
3′,5′-Dimethoxy-4-stilbenol

Mechanisms:

    • Powerful antioxidant and anti-inflammatory compound[1]
    • Higher bioavailability, half-life and potency than resveratrol – crosses the blood brain barrier efficiently to act as a cerebral antioxidant[1]
    • Inhibits the synthesis of pro-inflammatory molecules such as PGE2[1]
    • Decreases neuroinflammation by inhibiting IkBα
    • Decreases age-related cognitive decline – possibly through protecting dopamine levels[1]
    • Modifies AMPK levels and activates SIRT1 genes associated with caloric restriction and life extension[1]
    • Anxiolytic effects through regulation of ERK phosphorylation[2]
    • Lowers blood glucose and cholesterol levels[3]
References

[1] Poulose SM, et al (2015). Effects of pterostilbene and resveratrol on brain and behavior. Neurochem Int, 89:227-33. doi: 10.1016/j.neuint.2015.07.017
[2] Al Rahim M, et al (2013). Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation. Planta Med, 79(9):723-30. doi: 10.1055/s-0032-1328553
[3] Estrela JM, et al (2013). Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci, 50(3):65-78. doi: 10.3109/10408363.2013.805182