GLYCINERGIC PRODRUGS

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Vitamin B15, or pangamic acid was used by Russian swimmers during the Olympics. It is used to treat a host of diseases of the skin, respiratory tract, nerves and joints. Two of the constituents of this non-vitamin though, are glycine and N,N-dimethyl glycine (DMG).

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The amino acid glycine is an inhibitory neurotransmitter in the brain. Glycine potentiates receptor neurotransmission thus inhibiting the dopaminergic neurons in the substantia nigra. Phencyclidine (angel dust) is an NMDA antagonist that causes psychosis.

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Glycine, DMG and D-cycloserine (a glycinergic agonist) have all been explored as potential treatments for schizophrenia because they are NMDA augmenters.

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Glycine exerts a profound inhibitory effect on non-dopaminergic cells in the substantia nigra. 

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DMG is widely available and supposed to be able to stimulate the immune system and improve athletic endurance.

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The autism community has claimed DMG reduced the behavior problems in autistic children.

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D-cycloserine is thought to be a “nootropic” drug, a cognitive enhancer, on the basis of preclinical studies and clinical studies in patients with Alzheimer’s disease 82). It may also have anti-seizure potential (83-85). D-cycloserine was found to enhance recovery from 7 experimental TBI in rats (86). A multi-center, controlled study of gavestinel, a selective glycine agonist, had no more effect than placebo in 1367 patients with ischemic stroke (87). D-cycloserine is a prescription drug, but glycine and DMG are freely available over-the- counter. Physicians, then, are likely to encounter patients who are taking DMG, or giving it to their children, in hopes that it will correct a cognitive or a developmental weakness. It is probably a harmless drug, if one can call it a drug, and it is not an outlandish thing to try, but there is little scientific evidence to support its use. It is a good idea to pursue investigations of NMDA activators like the glycinergic “prodrugs,” but there is no basis for recommending them to patients at this time.

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Oxidative Stress is the uncontrolled production of free radicals. This type stress is the primary cause of diseases like Parkinson''s and Alzheimers''.  What that means for healthy people is that oxidative stress accelerates aging. Minimizing damage with antioxidants is one way to do that.

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Minimizing free radical production and neutralizing them with more antioxidants is the core of this anti-aging strategy. 

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Lipid peroxidation by free radicals is responsible for the deteriorating process that results in dysfunction. These illnesses include atheroschlerosis, arthritis, and cataracts.  These attacks occur in the body, not the brain.

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Oxidative stress in the brain is linked to neuronal degeneration which leads to stroke, brain dysfunction and aging. Preventing these attacks is one of the goals of smart drugs.

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Highly metabolic tissues, brain and muscle, increase oxygen consumption which creates oxygen radicals. These free radicals are produced during oxgen use. Their removal is dependent on the body''s scavenging system. Augmenting this system is another goal of smart drugs.

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Tissue damage due to oxidative stress accumulates with age.  Since the damage they cause is so fundamental there is no limit to its potential destructive force.

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Oxidative stress can be minimized by antioxidants and it follows that the conditions associated with aging, like atheroschlerosis, dementia, and arthritis can also be minimized.  

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The nootropic effect of a diet, rich in antioxidant micronutrients, is improved nerve transmissions. This is based on quencing free radicals before they can upset transmissions.

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The body''s antioxidant defense systems includes the enzymes superoxide dismutase, catalase and glutathione peroxidase. They along with Vitamins C and E work synergisticaly to neutralize free radicals. There effectiveness in the brain 

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Therapeutic attention has been directed to agents that function in the role of free radical scavengers or those that augment those already present.  This includes  retinoic acid (Vitamin A, beta-carotene), deprenyl or selegiline, a MAO-B inihibitor, gingko biloba, selenium, zinc and riboflavin. A powerful group of compounds thought to fortify the body''s scavenging system.

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