Neuroprotectives

Neuroprotectives are classes of chemical agents used in research into combatting neurological degeneration and protection against secondary brain injury. Geroprotectors are specifically aimed at minimizing the consequences of aging with the ultimate aim of promoting life-extension.

The information available to researchers from around the world has been conveniently structured in websites relevant to the research aims. Two good sources of information about neuroprotectives and geroprotectors are Neuroprotective Agents: List of Drugs & Supplements (http://mentalhealthdaily.com/2015/02/17/neuroprotective-agents-list-of-drugs-supplements/) ,¹ and geroprotectors.org² – the Curated Database of Geroprotectors. Please read on for more information about protective agents.

Neuroprotectives

Neuroprotection refers to the aim of preserving neuron function and structure in response to a CNS-insult (acute injury or chronic disease). Neuroprotective agents aim to offer a form of protection against neuronal injury or the degeneration of neurons caused by diseases like Parkinson’s, Alzheimer’s, or Multiple Sclerosis.

An important aspect of neuroprotective substances involves the management of secondary brain injury, as a result of the initial CNS insult. This can be the result of traumatic brain injury or acute neurotoxicity (for example, methamphetamine overdose), or the result of chronic degenerative diseases. Secondary brain injury refers to the changes that occur in the brain as a result of an initial CNS injury.

Aspects of secondary brain injury include a decreased function of calcium ion channels and calcium overload in mitochondria, a sustained reduction of protein synthesis, and initiation of endogenous apoptosis mechanisms.³ Another important aspect of secondary CNS injury involves gliosis – the change in structure and function of glial cells, which are now known to be highly involved in CNS function.⁴

There are multiple factors that can cause CNS injury – including diseases, acute toxins, and brain injury. A list of the most common causes of CNS injury includes:

1. Brain cancer (specifically glioma)
2. Acute injury (neck / head / spine)
3. Stroke
4. Neurotoxins
5. Chronic degenerative diseases⁵

Neuroprotection is a well-studied form of neuroscience research. More funding is being allocated and more research is being conducted into neuroprotective substances and the science of neuroprotection as technology in this field increases.

The primary objective of a neuroprotective substance is to limit or prevent neuronal dysfunction/degeneration after CNS injury.

There are a number of different categories of neuroprotective substances, which include:

1. Antioxidants
2. Anti-inflammatories
3. Apoptosis inhibitors
4. Neurotrophic substances
5. Ion channel modulators
6. Others⁶

Geroprotectors

While neuroprotectors aim to prevent the degeneration of nerve cells, geroprotectors are used to combat the effects of aging and age-related diseases. Geroprotectors are functional substances that have been shown to extend the lifespan of animals, and may have future relevance in human research and therapy. Geroscience is predicted to become a key concept in biomedicine as aging research increases.⁷

The process of aging is fundamental to all living organisms. In fact, life itself can be defined simply as the process of aging.⁸ This process of aging is highly conserved throughout living organisms, and especially in the animal kingdom.

Similar genes are expressed in all living species including bacteria, yeast, nematodes, fish, and mammals. The aging mechanism includes a number of genes and physiological processes. For example:

1. Insulin like Growth Factor (IGF-1) signaling
2. Free-radical ions
3. Forkhead box (FOXO) transcription factors
4. Senescence-promoting genes
5. Sirtuin (SIR-2) / SIRT 1 transcription factors
6. Heat shock proteins
7. Mammalian TOR enzymes⁹

Geroprotectors, therefore, aim to target one or more of these processes to minimize the process of aging and to increase life-expectancy. According to geroprotectors.org:

“A “geroprotector” is any intervention that aims to increase longevity, or that reduces, delays or impedes the onset of age-related pathologies by hampering aging-related processes, repairing damage or modulating stress resistance.”¹⁰

The Geroproctors.org website offers a curated database of geroscience research with over 250 geroprotection experiments listed, and information on over 200 chemicals that may support life-extension and suppression of aging mechanisms.

Geroprotection is a relatively new science and more research is required to develop patentable products with well-documented life-extending properties.

One interesting form of geroprotection is calorie restriction. A study originally published around 80 years ago from the University of Sydney’s Charles Perkins Centre showed that a low-protein, high carbohydrates diet prolonged the lives of rats. This diet also included cutting calorie intake by around 40%. Since the time of the publication, numerous studies have found similar results – a low calorie, low protein, high carbohydrates diet may be effective at promoting life-extension in mammals.¹¹

NewMind Neuroprotectives / Geroproctectors

1. Centrophenoxine HCl, ≥98%

Centrophenoxine HCl (Lucidril) is a cholinergic compound with an attached DMAE (dimethylaminoethanol) group that offers enhanced DMAE transport into the brain. Research suggests that Centrophenoxine HCl is effective at reversing some of the symptoms of aging, including the removal of waste products from the brain and acting as a general cognitive enhancer.¹²

2. D-cycloserine, ≥90%

D-cycloserine (DCS) is a partial glutamatergic NMDA agonist, and is often used for research into prevention of anxiety and other psychological disorders. Clinical studies have shown that DCS may be useful for exposure-related treatment of numerous psychological disorders. However, the optimal dose, dose timing, drug-drug interactions, long-term effects, and specificity of cognitive processes targeted by DCS are yet to be established.¹³

Further studies have indicated that D-cycloserine may be effective as a neuroprotective substance by reestablishing long-term potentiation after brain trauma. The neuroprotective effects are suggested to be an outcome of DCS’s NMDA receptor interaction.¹⁴

3. Aniracetam, ≥99%

Aniracetam is a molecule from the racetam family with potent cholinergic properties. Aniracetam is a positive modulator of AMPA glutamate receptors, and may decrease desensitization of receptors. Evidence suggests that aniracetam may help to reduce damage to memory and learning caused by various neurotoxins. Furthermore, aniracetam is currently being studied for its neuroprotective effects in the management of stroke and degenerative diseases.¹⁵

4. Noopept, ≥98%

Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is a well-known neuroprotector and Nootropic substance. It is most often used in research for cognitive enhancement and the prevention of disease-related cognitive decline. Noopept also has a history of being used by otherwise healthy individuals to improve cognitive performance.¹⁶

Animal studies have shown that single Noopept doses increased NGF and BDNF mRNA concentrations in the brain. Research has suggested that modulation of these factors (neurotrophins) may reduce the cognitive decline and memory impairment associated with degenerative diseases and aging.¹⁷

5. Oxiracetam, ≥99%

Oxiracetam is another racetam compound with a similar mechanism of action to that of aniracetam. Oxiracetam is a positive AMPA receptor modulator and may additionally increase glutamate, acetylcholine, and D-aspartic acid release.¹⁸

Studies have shown that pre-treatment of oxiracetam prevents neuronal degeneration in response to trimethyltin treatment in adult male rats.¹⁹ In addition, Oxiracetam has been suggested to increase long-term potentiation – possibly as a result of increasing glutamate and D-aspartic acid concentrations.²⁰ This is the basis from which additional studies into oxiracetam’s neuroprotective abilities may be developed.

6. Phenylpiracetam, ≥99%

Phenylpiracetam is a derivative of the original racetam compound, Piracetam, and involves the simple addition of a phenyl-group to improve absorption and efficiency. Phenylpiracetam is considered as a Nootropic substance and has psychostimulatory effects. Limited studies make drawing conclusions about Phenylpiracetams’ neuroprotective effects difficult. Studies suggest possible anti-inflammatory effects as well as potential glutamatergic action.²¹

7. Pramiracetam, ≥99%

Pramiracetam is a derivative of piracetam with limited clinical research available. Pramiracetam is primarily used in research for cognitive performance enhancement. Studies have suggested that pramiracetam may have adrenergic effects and it is sensitive to corticosteroid concentrations. Animal studies have indicated the potential of pramiracetam in restoring EEG function in animals suffering from neuronal injury.²²

Natural Neuroprotective Agents / Anti-Aging Supplements

As awareness of the importance of neuroprotection grows, there is an increasing demand for natural neuroprotective agents and anti-aging supplements by consumers. The chemicals listed above are for research purposes only – to be used in clinical laboratory settings by professionals. However, many people with limited access to equipment or expertise in neuroscience research are still interested in experimenting with neuroprotectives and geroprotectors.

Some substances with research indicating neuroprotective or geroprotective effects are available to purchase online as dietary supplements. Many of these can be bought from renowned supplements vendors like Liftmode.com. These include anti-aging supplements and the best Berberine supplements. Examples of natural neuroprotective agents include:

1. Caffeine + L-Theanine²³
2. Quercetin²⁴
3. Baicalin²⁵
4. Green Tea Extract²⁶
5. Choline Bitartrate²⁷
6. Huperzine A²⁸
7. Berberine²⁹

According to the latest research, most natural neuroprotective agents can be classed as antioxidants or anti-inflammatories. Other classes of neuroprotectives / geroprotectors include immunosuppressive calcineurin inhibitors, NOS inhibitors, sigma-1 modulators, AMPA agonists, and calcium ion channel blockers.³⁰

Further research has suggested that the cannabinoids found in marijuana may contain a number of neuroprotective abilities. The major alkaloids studied were cannabidiol and delta 9-tetrahydrocannabinol, which both reduced NMDA, AMPA and kainate receptor-mediated neurotoxicities.³¹

Toxicity and Warnings

Neuroprotectives and geroprotectors may have toxic effects at high doses. Studies into the long-term effects of these chemical agents are still limited and further research is warranted. Please read through the product category descriptions for more information about the toxicity of specific Newmind neuroprotectives and geroprotectors.

Please note that NewMind compounds are solely for research purposes and are strictly not for human consumption, human clinical trials, or veterinarian research.

¹ International Conference on Neuroprotective Agents - http://neuroprotective.org/, retrieved on March 29, 2017

² Geroprotectors: Curated database: 'CURATED DATABASE OF GEROPROTECTORS’ - http://geroprotectors.org/, retrieved on March 29, 2017

³ Siesjö BK, Siesjö P, “Mechanisms of secondary brain injury”, Eur J Anaesthesiol. 1996 May;13(3):247-68. 

⁴ MDDK: Online Medical Doctor, “Gliosis”, retrieved on March 29, 2017

⁵ Research Areas: Cores to Translate Therapies, University of Florida McKnight Brain Institute, UFHealth online, retrieved on March 29, 2017

⁶ “What is neuroprotection?”, by Christian Nordqvist, September 2014, Medical News Today 

⁷ “About: Geroprotectors”, Geroprotectors.org, retrieved on March 29, 2017

⁸ ZD Sharp, “Aging and TOR: interwoven in the fabric of life”, Cell Mol Life Sci. 2011 Feb;68(4):587-97. doi: 10.1007/s00018-010-0542-0 

⁹ N Magon, Navneet, Sanjiv Chopra, and Pratap Kumar. “Geroprotection: A Promising Future.” Journal of Mid-Life Health 3.2 (2012): 56–58. PMC. Wealth 3.2 (2012): 

¹⁰ 56–58. PMC. Web. 29 Mar. 2017. A Moskalev et al., “Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease”, Aging (Albany NY). 2015 Sep;7(9):616-28.

¹¹ SM. Solon-Biet et al., “Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice”, Cell Reports, Volume 11, Issue 10, p1529–1534, 16 June 2015

¹²  “Centrophenoxine”, Examine.com, retrieved on March 29, 2017

¹³  SG Hofmann, “D-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders”, Biol Mood Anxiety Disord. 2013; 3: 11, Published online 2013 Jun 15. doi:  10.1186/2045-5380-3-11

¹⁴ R Yaka et al., “D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury”, FASEB J. 2007 Jul;21(9):2033-41. Epub 2007 Mar 9

¹⁵ “Aniracetam”, Examine.com, retrieved on March 29, 2017

¹⁶ “Noopept”, Examine.com, retrieved on March 29, 2017

¹⁷ RU Ostrovskaya et al., “Noopept stimulates the expression of NGF and BDNF in rat hippocampus”, Bull Exp Biol Med. 2008 Sep;146(3):334-7.

¹⁸ “Oxiracetam”, Examine.com, retrieved on March 29, 2017

¹⁹ Hlinák Z, Krejcí I, “Oxiracetam pre- but not post-treatment prevented social recognition deficits produced with trimethyltin in rats”, Behav Brain Res. 2005 Jun 20;161(2):213-9. Epub 2005 Mar 31.

²⁰ M Raiteri et al., “Effects of oxiracetam on neurotransmitter release from rat hippocampus slices and synaptosomes”, Neurosci Lett. 1992 Sep 28;145(1):109-13 

²¹ “Phenylpiracetam”, Examine.com, retrieved on March 29, 2017  

²² “Pramiracetam”, Examine.com, retrieved on March 29, 2017

²³ P Bagga et al., “Neuroprotective effects of caffeine in MPTP model of Parkinson's disease: A (13)C NMR study”, Neurochem Int. 2016 Jan;92:25-34. doi: 10.1016/j.neuint.2015.11.006

²⁴  LG Costa et al., “Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More”, Oxidative Medicine and Cellular Longevity, Volume 2016 (2016), Article ID 2986796, 10 pages 

²⁵ YF Liu et al., “The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats”, Neurochem Res. 2012 Aug;37(8):1670-80. doi: 10.1007/s11064-012-0771-8

²⁶ T Kakuda, “Neuroprotective effects of the green tea components theanine and catechins”, Biol Pharm Bull. 2002 Dec;25(12):1513-8.

²⁷  AA Borges et al., “Neuroprotective effect of oral choline administration after global brain ischemia in rats”, Nutritional Neuroscience, An International Journal on Nutrition, Diet and Nervous System, Volume 18, 2015 - Issue 6 

²⁸ U Damar et al., “Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research”, Expert Rev Neurother. 2016 Jun;16(6):671-80. doi: 10.1080/14737175.2016.1175303

²⁹  EN Simões Pires, “Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved”, Brain Res. 2014 Apr 4;1557:26-33. doi: 10.1016/j.brainres.2014.02.021 

³⁰ Levi MS, Brimble MA, “A review of neuroprotective agents”, Curr Med Chem. 2004 Sep;11(18):2383-97

³¹ AJ Hampson et al., “Neuroprotective antioxidants from marijuana”, Ann N Y Acad Sci. 2000;899:274-82.