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Old 07-18-2012, 09:26 AM #1
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Supplement Science Thread-Sciencey Talk

Instead of bombarding the supplement thread with studies and causing certain users to dig through information they don't care about, lets do it in here.
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Old 07-18-2012, 09:26 AM #2
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Matt/Lurker, though you my be interested

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Introduction
Piracetam is a derivative of GABA which was originally designed to be an anxiolytic. Later testing revealed that it had no sedative or GABAergic effects, however it demonstrated an ability to enhance learning and cognition in some animal models. Further studies revealed a global cerebroprotective effect in the context of dementia, hypoxia, and other brain impairments.

In addition to its lack of GABAergic activity, it also lacks dopaminergic, anticholinergic, and antihistaminergic activity. Its one notable receptor interaction includes glutaminergic modulation at the NMDA and AMPA receptors.

Pharmacodynamics
Piracetam's ability to positively modulate the glutamate NMDA channel has been known for decades, however its ability to interact with the AMPA receptor is a fairly new discovery (1). Although piracetam binds to the AMPA receptor with a much lower affinity than the ampakines or aniracetam, it can bind to multiple sites on the AMPA receptor and may potentiate the effects of these agents acting on the AMPA receptor. Similarly, positively modulating the AMPA receptor itself increases the activation of the NMDA receptor, and so piracetam can be considered to be somewhat self-potentiating.

CNS Activity
Although piracetam does not directly activate any receptor, it positively modulates certain CNS glutaminergic receptors through allosteric activation. Allosterism is a dynamic method of facilitating receptor activation by binding to a receptor subunit that is distant from the agonist binding site. One of the advantages of allosteric activation is that it supports receptor activation even in the presence of physiological receptor antagonists (barbiturates, benzodiazepines, alcohol). Similarly, allosterism prevents receptor over-activation in the presence of excessive agonist (glutamate). The latter characteristic is one of the modalities by which piracetam helps to prevent brain excitotoxicity in the context of hypoxia or traumatic brain injuries.

The NMDA receptor is a voltage-dependent ion channel that allows calcium to enter the neuron along its concentration gradient after activation by glutamate and glycine (or D-serine). Normally, this channel is blocked by a positively charged magnesium ion which is attracted to the negatively charged intracellular compartment. In order for the magnesium ion to be displaced, the intracellular environment must possess a net positive charge.



This circumstance is made possible when glutamate first activates the AMPA channel. These channels then allow the rapid influx of positively charged sodium ions which results in a temporary reversal of polarity of the intracellular compartment.



After influx through the NMDA channel, ionic calcium is able to activate various enzymes including those that increase the transcription of various genes.

The Theory
The NMDA receptor is intricately linked to memory encoding and storage. As mentioned above, activating the receptor causes the transcription of products responsible for neuronal plasticity, growth, and survival. These include the growth hormone Brain Derived Neurotrophic Factor (BDNF) and its receptor trkB (4, 5, 6, 7). Increasing BDNF is one of the mechanisms by which antidepressants reverse depression. Similarly, agents which potentiate the NMDA receptor (via potentiating the AMPA receptor) have demonstrated cognitive enhancing abilities in normal non-human primates, as well as the ability to completely reverse sleep deprivation (8, 9). Conversely, NMDA antagonists like ketamine and phenylcyclidine are well known to disrupt cognition, and impair memory formation.

In addition to enhancing glutaminergic neurotransmission, piracetam also effects, and is effected by, the cholinergic system. This system consists of 2 families of receptors (metabotropic & ionotropic) and its ligand, acetylcholine (Ach). In dementia and cognitive decline, both types of receptors are diminished along with the production of acetylcholine. The reason for the latter is due to a generalized death of acetylcholine producing neurons in the hippocampus, and due to diminished production of the enzyme choline acetyl transferase. The latter is responsible for the reason that supplementing with acetylcholine precursors has little impact on cognition in dementia, whereas compounds that prevent the degredation of acetylcholine (Acetylcholinesterase Inhibitors) markedly improve dementia symptoms.

One of the reasons why acetylcholine is able to improve cognition and memory is due to its effects on the NMDA receptor. Specifically, agonizing the M1 acetylcholine receptor enhances the responsiveness to NMDA stimulation by causing the pre-synaptic release of glutamate (10). Similarly, agonism of nicotinic Ach (nAch) receptors on post-synaptic neurons synergizes with the AMPA receptor in reversing the polarity of the intracellular environment, thereby encouraging NMDA activation (11). The densities of both types of receptors are diminished in dementia and mild-cognitive decline. In rats, piracetam has demonstrated the ability of restoring metabotropic Ach receptors in the frontal cortex of aged rats, along with facilitating the release of acetylcholine in the hippocampus (2). In another rat experiment, combining choline and piracetam together resulted in a profound enhancement of memory formation versus either compound used alone (13).


The Reality
Unfortunately, piracetam has never demonstrated a clear benefit in healthy humans. Even in mice studies, young healthy animals are generally immune to the effects of piracetam (2). The reason for this dichotomy is due to piracetams low potency at the NMDA receptor, and even lower potency at the AMPA receptor. Since the NMDA receptor is reliant upon the AMPA receptor for activation, piracetam is pharmacodynamically challenged.

As recent studies have demonstrated, the main modality by which piracetam is now thought to enact its cerebroprotective effect is by enhancing the fluidity of the lipid bilayer; specifically, the fluidity of the mitochondrial membrane (3). The exact mechanism for this characteristic is unknown, although we do know that piracetam possesses no radical scavenging properties.

In the aged brain, complexes I and IV of the electron transport chain (ETC) become less active and result in the unchecked production of reactive oxygen species (ROS) which ends up damaging the DNA and cell membrane. Piracetam has been shown to increase the activity of both complexes and it has been suggested that this characteristic may support mitochondrial longevity.

In addition to supporting the energetic needs of the neuron, the mitochondria also regulates intracellular calcium and prevents it from activating deleterious enzymes and cascades. As discussed above, piracetam is an allosteric regulator of the NMDA channel and prevents excessive calcium influx. Similarly, by restoring the fluidity of the mitochondrial membrane, piracetam enhances the mitochondrial's ability to sequestor calcium.

The vast majority of healthy adults who use piracetam have sufficient mitochondrial membrane fluidity, and therefore piracetam's ability to enhance cognition through this mechanism is muted.

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Old 07-18-2012, 09:27 AM #3
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Enhancing the Effects of Piracetam
Piracetam has multiple known mechanisms for encouraging memory formation and cognition. Unfortunately, most of the effects are only observed in the context of abnormal brain function. Luckily, due to recent studies which have more comprehensively examined the mechanisms behind piracetam, it is possible to increase the effects of piracetam through synergisms.

As noted above, piracetam has been shown to increase the activity of Complexes I and IV of the ETC. Piracetam has also been shown to support mitochondrial longevity and function by enhancing membrane fluidity.




Coenzyme Q10 (CoQ10) is a fat soluble compound which participates in the ETC as an electron acceptor from Complex I and II. Relative deficiencies of CoQ10 have generalized deleterious effects on the body, mostly as a result of mitochondrial dysfunction. Supplemental CoQ10 has a multitude of health benefits including limiting membrane peroxidation, and reducing ROS formation. The latter two mechanisms would naturally support mitochondrial longevity and function, and synergize well with piracetam. Co-supplementing with Vitamin E helps to regenerate the active form of CoQ10, ubiquinol from its oxidized form, ubiquinone. There is also some evidence that the combination increases tissue retention of CoQ10 (14). Keep in mind that these effects would require chronic supplementation in order to be observed, and that the effects will be much more pronounced in those experiencing progressive memory decline.

The next mechanism by which piracetam may enhance cognition is by supporting cholinergic neurotransmission. Studies have shown that piracetam increases the density of metabotropic acetylcholine receptors in the cerebral cortex, and that it facilitates neuronal acetylcholine release in the hippocampus. The former mechanism may support attention and working memory through norepinephrine release and the latter may support cognition by downstream mechanisms involving the NMDA receptor. Acetyl-L-Carnitine (ALCAR) has been shown to increase the production of metabotropic glutamate receptors in various parts of the brain, although not in the hippocampus. The significance of this effect is unclear, especially in relation to cognition. One of the biggest mechanisms by which ALCAR may synergize with piracetam is by enhancing the production of acetylcholine by amplifying the enzyme choline acetyl transferase (15).




As mentioned above, the aged and demented brain has a diminished production of choline acetyl transferase. This enzyme is responsible for converting acetylcholine precursors into acetylcholine. Without an ability to maintain an acetylcholine reserve, Ach receptors slowly down-regulate resulting in self-perpetuating cognitive deterioration. Futhermore, since Ach receptors are intimately linked to the glutaminergic system, a decrement in Ach or Ach receptors will result in diminished BDNF production, thereby removing the signal for neuronal growth and survival.



Summary
Piracetam is the grandfather of nootropics and has been studied for the last 50 years. The effects of piracetam are subtle, even in the context of brain pathology. There is some evidence that its beneficial effects may accumulate over longer periods of time. The dosage of piracetam required to meet the minimum threshold for physiological significance is 5 grams per day. In order to maximize the effects of piracetam, the addition of CoQ10, Vitamin E, and ALCAR, should warrant contemplation. Similarly, supplementing with a choline source (Lecithin, CDP-Choline, Alpha-GPC) is a logical assumption based on the mechanisms proposed above, in addition to the rat study which demonstrated synergism. Utilizing an acetylcholine esterase inhibitor (AchEi) is a more advanced protocol and will be discussed in the next article.


References
(1) http://www.ncbi.nlm.nih.gov/pmc/arti...7/?tool=pubmed
(2) http://www.springerlink.com/content/r2n324624xt644j7/
(3) http://www.ncbi.nlm.nih.gov/pubmed/9037245
(4) http://www.ncbi.nlm.nih.gov/pubmed/20095391
(5) http://www.sciencedirect.com/science...80450469008299
(6) http://www.ncbi.nlm.nih.gov/pmc/arti...6/?tool=pubmed
(7) http://www.ncbi.nlm.nih.gov/pubmed/12663749
(8) http://www.ncbi.nlm.nih.gov/pubmed/16104830
(9) http://www.ncbi.nlm.nih.gov/pubmed/22054117
(10) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33643/
(11) http://jpet.aspetjournals.org/content/280/3/1117.short
(12) http://www.sciencedirect.com/science...91305784902168
(13) http://www.sciencedirect.com/science...97458081900075
(14) http://jn.nutrition.org/content/130/9/2343.short
(15) http://www.ncbi.nlm.nih.gov/pubmed/7563233
(16) http://www.ncbi.nlm.nih.gov/pmc/arti...6/?tool=pubmed
...
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Old 07-18-2012, 09:27 AM #4
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Phenylpiracetam:

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Several selected publications on phenylpiracetam that we cite here are from Russian journals, which are not in PubMed. We reviewed, without a selection bias, key and core articles that demonstrate evidence-based clinical investigations and other available information on marketed products, clinical findings, non-clinical biochemical and pharmacological data, and promising piracetam-like drugs with unknown benefit-risk profiles. 2.

Marketed Products There are six relevant medications on the market worldwide (table II). Piracetam and levetiracetam were developed by UCB Pharma, Belgium; oxiracetam by ISF, Italy; aniracetam by Roche Pharmaceuticals, Switzerland; pramiracetam by Warner-Lambert, USA;[6] and phenylpiracetam by the Medical-Biological Institute of the Russian Academy of Sciences (manufactured by Valenta Pharmaceuticals, Russia).

In 2003, the State Pharmacological Committee of Russia approved phenylpiracetam as a prescription drug for cerebrovascular deficiency, depression, apathy, attention and memory decline, and it is recommended for cosmonauts for increasing physical and mental/cognitive activities in space.[7]

The affinity of phenylpiracetam to the nicotinitic acetylcholine (nACh) receptor, but not the glutamate NMDA subtype, was demonstrated in ligandbinding experiments in vitro. However, injection of this drug (100 mg/kg, intraperitoneally) to rats increases the numbers of both nACh and NMDA receptors, but decreases serotonin and dopamine receptors in the brain tissue.[40]

Phenylpiracetam A phenyl derivative of piracetam, phenotropil or phenotropyl is absorbed fast and exhibits high oral bioavailability (Phenotropil?, product insert). Studies on rodents (100 mg/kg, intramuscular, oral) showed absorption time of <1 hour and half-life of 2.5–3 hours,[19,20] but its pharmacokinetic profiles in humans are unpublished. It ? 2010 Adis Data Information BV. All rights reserved.

Phenylpiracetam A phenyl derivative of piracetam, phenotropil or phenotropyl is absorbed fast and exhibits high oral bioavailability (Phenotropil?, product insert). Studies on rodents (100 mg/kg, intramuscular, oral) showed absorption time of <1 hour and half-life of 2.5–3 hours,[19,20] but its pharmacokinetic profiles in humans are unpublished. It ? 2010 Adis Data Information BV. All rights reserved.

Phenylpiracetam is reportedly beneficial to people who develop cognitive deficits and/or depression after encephalopathy and brain injures (table V). It increased quality of life in patients with encephalopathy after acute lesions (30 people), brain traumas (33 people) and gliomas surgery (36 people). The average minimental state examination (MMSE) scores (a standard 30-point questionnaire used to assess cognition) from baseline improved in all groups. In the end, anxiety improved and depression declined substantially, and that resulted in less discomfort and better ability to execute everyday activities.[85] Recovery of memory, attention and sensomotor disturbances were indistinguishable for similar treatments in mild cranial brain traumas. The differences noted favoured phenylpiracetam over piracetam because of faster alleviation of headaches and a general fatigue after 7 and 14 days.[86]

Phenylpiracetam was favoured in the treatment of chronic vascular encephalopathy as it improved the cognitive performance in all tests, whereas only two of the eight test scores increased in the piracetam arm.[87] It also improved both asthenia and depression scores, albeit to a lesser extent in MS patients.[88] In a comparative trial, asthenia and chronic fatigue syndrome (CFS) patients were treated with phenylpiracetam (68 people), piracetam (65 people) and placebo (47 people). The scores of the ten-word memory test and attention switching tests for the phenylpiracetam improved relative to those of piracetam and placebo. Overall, 83% of asthenic and 87% of CFS patients responded well to phenylpiracetam versus 48% and 55%, respectively, to piracetam.[89]

In agreement with this, phenylpiracetam markedly increased the problem-solving skills of adolescents with asthenia who were A-players, B-players and C-players (i.e. the number of individuals able to respond to the memory and attention tests after the first, second and third attempts) from 11%, 15%, 73% before to 23%, 40%, 37% after treatment, respectively. It was superior to piracetam Drugs 2010; 70 (3) Table V.

Piracetam-like compounds in clinical development Sponsor/study site Intent to treat Study design No. of pts (age in y) Dosage (mg/d, oral) (2)600 Trial duration Outcome measures Efficacy summary (% improvement rate) Tx 86 Cx 60 Adverse event References ? 2010 Adis Data Information BV. All rights reserved.

Drugs 2010; 70 (3) 300 Pramiracetam Army Central Hospital, Kiev, Ukraine Cognition/memory deficits (after TBI) Active (piracetam) controlled 65 (16–60, mean 31) 1 mo Amnesia and orientation NA 84 Phenylpiracetam Omsk State Medical Academy, Russia Encephalopathy (gliomas to acute lesions) Open-label 99 (40–60) 200 1 mo MMSE Anxiety Depression Tx 45 – 16 50 – 5 38 – 4 None 85 Navy Hospital, Vladivostok, Russia Encephalopathy (after TBI) Active controlled 56 (20–30) (2)100 1 mo Asthenia, headache ND None 86 Nizhny Novgorod State Medical Academy, Russia Encephalopathy (vascular) Active controlled 51 (mean 57.2) (2)200 1 mo Neurological and psychological Tx 32 – 11 Cx 25 – 11 None 87 Multiple Sclerosis Center of Novosibirsk, Russia Multiple sclerosis Open-label 39 200 1 mo Asthenia Anxiety Depression 11 20 21 Sleep disturbance 88 National Research Center for Social and Forensic Psychiatry, Moscow, Russia Asthenia/fatigue syndrome Active and placebo controlled 180 (21–40, mean 25 (3)100–200 1 mo Memory (10-word test) Tx 88 – 52 Cx 37 – 19 PL 16 – 13 None 89 Clinic No. 28, Volgograd, Russia Asthenia Active controlled 39 (14–19, mean 15) (2)100 1 mo Problem solving ND None 90 Malykh & Sadaie Ural State Medical Academy, Chelyabinsk, Russia Epilepsy rpc 61 (mean 29.7) (2)100 2 mo Seizure: Total no. Frequency Tx 46 – 1 46 – 3 None 91 Continued next page Table V. Contd Sponsor/study site Intent to treat Study design No. of pts (age in y) 40 (17–20) Dosage (mg/d, oral) (2)100 Trial duration 1 mo Outcome measures MMSE Efficacy summary (% improvement rate) 12 Adverse event None References ? 2010 Adis Data Information BV. All rights reserved. Drugs 2010; 70 (3) Piracetam and Related Drugs for CNS Disorders Gorbunov Hospital, Kemerovo, Russia Epilepsy rpc 92 Tver State Medical Academy, Russia Cerebral stroke Open-label 20 (31–67, mean 52) 100 1 mo Ab titres: MMP PHL Tx 34 – 4 7.5 – 0.6 None 93 Regional Neurologic Department, Moscow, Russia Cerebral stroke (ischaemic) Open-label 120 (3)100, 200 1 mo MMSE Barthel index Stroke scale Tx 10 – 0.4 6 – 0.4 9.1 Nausea (3%) 94 Orel State University, Russia Glaucoma Open-label 26 100 1 mo Vision acuity Tx 16 – 8 None 95 Nefiracetam Daiichi Sankyo, Tokyo, Japan; Prestwick Clinical, Washington, DC, USA Poststroke depression rdbpc 159 (mean 66.8) (3)600, 900 12 wk Depression Apathy None Tx 34 PL 5 None 96 97 NINDS Alzheimer’s disease Open-label 50 (50–90) NA 20 wk NA NA NA 98 Rolipram NIMH Major depressive disorder rdbpc 50 (18–65) NA 3y Depression, PDE4 test NA NA 99 NINDS Multiple sclerosis Open-label 6 (18–65) 7.5–9 8 mo MRI None Poor tolerability 100,101 Ab = antibody; Cx = control; MMP = main myelin protein; MMSE = Mini Mental State Examination; MRI = magnetic resonance imaging; NA = not available; ND = not done (test scores lacking); NINDS = National Institute of Neurological Disorders and Stroke; NIMH = National Institute of Mental Health; PDE4 = phosphodiesterase type 4; PHL = phospholipids; PL = placebo; rdbpc = randomized, double-blind, placebo-controlled; rpc = randomized, placebo controlled; TBI = traumatic brain injury; Tx = test agent; (2)-, (3)- indicates parallel fixed doses. 301 302 Malykh & Sadaie (400 mg/day) in combination with multivitamins and physiotherapy.[90] It is unclear whether any particular patient(s) was unresponsive to or relapsed after therapy. Convulsion/Epilepsy, Seizure Phenylpiracetam exhibited an antiepileptic action in rodents. Its effective dose (300 mg/kg) decreased the metrazol (a drug used as a circulatory and respiratory stimulant)-induced seizure by 50%.[106] Phenylpiracetam was administered to patients in addition to one standard AED (including valproyl amide, carbamazepine, lamotrigine, topiramate or a barbiturate, or structured polytherapy with more than one of these drugs). It substantially mitigated the number and frequency of seizures of patients receiving AED only and the number of individuals with a desynchronous EEG profile decreased from eight to three, while the number of individuals with seizure remissions increased modestly.[91] Consistent with this, cognitive functions in epileptic patients based on an MMSE test improved to only a small extent.[92] These trials favoured phenylpiracetam as add-on medication for epilepsy (table V). Cerebral Stroke/Ischaemia ganglial cell death was the rationale of a recent trial.
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Old 07-18-2012, 09:28 AM #5
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RUSSIAN FENOTROPIL INSTRUCTIONS TRANSLATION:

Instructions on Fenotropil TAB.100MG Fenotropil number 10 - a new nootropic drug with psychoactive effects. It is recommended for CNS pathological states of various origins: cerebrovascular insufficiency, neurotic state, asthenic depression vyaloapaticheskie state in schizophrenia, abstinence in alcoholism and drug addiction. Can also be used to increase resistance to stress, in order to prevent the development of fatigue, etc.

The composition and the form of: Fenotropil tablets of 10, 20 or 30 pieces. in the package. 1 tablet contains Fenotropil Phenotropil (N-carbamoyl-methyl-4-phenyl-2-pyrrolidone), 50 or 100 mg.

Pharmacological properties: Fenotropil - nootropic, cerebroprotector, neurometabolic stimulator. Effects similar to Piracetam therapeutic focus. Fenotropil has a marked neuroprotective effect of a psychoactive, anticonvulsant, anxiolytic, analgesic, antihypoxic, antitoxic, and antihypertensive effects. Fenotropil has a direct activating effect on the integrative activity of the brain, contributes to the consolidation of memory, improves concentration and mental performance, facilitates the learning process, increases the rate of information transfer between the hemispheres of the brain, regulates the activation and inhibition of the central nervous system and improves mood. Fenotropil has a positive effect on the exchange of blood and brain, stimulates the oxidation-reduction processes, increases the body's energy potential at the expense of glucose utilization, improves regional blood flow in the ischemic brain regions.

Increases the content of noradrenaline, dopamine and serotonin in the brain, does not affect the levels of GABA, is not associated with either GABA or the GAMKB receptors, has no appreciable effect on the spontaneous electrical activity of the brain. The stimulating effect of Fenotropil manifested in its ability to provide a moderately pronounced effect on motor responses, to improve physical performance, expressed antagonism to the cataleptic action of neuroleptics, as well as in reducing the severity of ethanol and the hypnotic action of hexenal. Stimulating effect Fenotropil ideatornoy prevalent in the field. Fenotropil stimulates antibody production in response to the antigen, indicating that its immune-boosting properties, but at the same time, it does not contribute to the development of immediate hypersensitivity and does not alter the allergic inflammation of the skin caused by the introduction of foreign protein.

Fenotropil has adaptogenic action in various models of stress, normalize circadian biorhythm indicator sympathoadrenal system. Adaptogenic effect Fenotropil manifested in excessive mental and physical fatigue while, hypokinesia and immobilization at low temperatures, with information overload. Phenotropil effect occurs during a single application, which is very important for use in hazardous environments requiring immediate effect. During the course of Fenotropil marked improvement in vision, which is manifested in the increasing severity, brightness and field of view. In exchange application Fenotropil not develop drug dependence and tolerance, "withdrawal syndrome". Fenotropil no effect on respiration and the cardiovascular system, showing unspoken diuretic effect, has anoreksigennoy activity in exchange application. Fenotropil improves blood flow to the lower extremities. Fenotropil has no teratogenic, mutagenic, carcinogenic and embryotoxic properties. Toxicity - low lethal dose in the acute experiment is 800 mg / kg.

Pharmacokinetics: Fenotropil is rapidly absorbed, penetrates into the various organs and tissues, easily passes the blood-brain barrier. The absolute bioavailability after oral administration of 100%. The maximum concentration achieved in blood after 1 hour, half-life is 3-5 hours. Fenotropil not metabolized in the body and is excreted unchanged. Approximately 40% of the drug is excreted in the urine and 60% of the drug is excreted in the bile and sweat.

Indications: Fenotropil recommended as a nootropic drug with psychoactive effects in pathological states of the central nervous system of various origins: post-traumatic conditions and phenomena of chronic cerebrovascular insufficiency sosuditoy accompanied by deterioration in intellectual-mental function, reduced motor activity, asthenic syndrome against cerebrovascular disease, neurotic condition manifested apathy , increased exhaustion, decreased activity, in violation of attention, memory impairment, disorders of learning processes, asthenic, apathetic, adynamic shallow (easy to moderate) depression, shallow psycho syndromes seen intellectual disabilities and mnesticheskimi apatiko-abulicheskimi phenomena vyaloapaticheskie state with schizophrenia, seizure disorder, alcohol abstinence, alcoholism and drug addiction (to reduce fatigue, depression, and intellectual-mental disorders), also recommended: hypertension stage I-II, obesity (alimentary-constitutional origins), for the prevention of hypoxia, increase resistance to stress, correction of the functional state of the body in extreme conditions, to prevent the development of fatigue and improve mental and physical performance, correction daily biorhythms, inversion of the cycle "sleep-wake" (the intersection of 4 or more time zones).

Dosage and Administration: inside. Dosage and set individually. Fenotropil taken orally immediately after meals. Do not take Fenotropil later than 15 hours. The average single dose of 150 mg (from 100 mg to 250 mg), the average daily dose is 250 mg (from 200 mg to 300 mg). The maximum permissible dose is - 750 mg per day. It is recommended to divide the daily dose into 2 doses. The daily dose is 100 mg taken once in the morning, and more than 100 mg daily dose is divided into two doses. Duration of treatment can vary from 2 weeks to 3 months. The average duration of treatment is 30 days. If necessary, the course may be repeated a month later. In order to increase efficiency - 100-200 mg once in the morning, within 2 weeks (for athletes - 3 days).

Recommended duration of treatment for patients with alimentary-constitutional obesity is 30-60 days at a dose of 100-200 mg once a day (morning). Overdose: No cases of overdose were reported. Treatment: symptomatic therapy.

Contraindications: Individual intolerance. Use during pregnancy and lactation: Fenotropil should not be administered during pregnancy and breastfeeding due to lack of data from clinical studies. Side Effects: Overstimulation, sleep disturbance (insomnia), autonomic dysfunction (flushing of the skin, a feeling of warmth), increased blood pressure. Cautions and precautions Fenotropil used with caution in patients with severe organic lesions of the liver and kidneys, severe hypertension, in patients with atherosclerosis, and patients who had undergone previous panic attacks, anxiety raptoidnye condition or acute psychotic states, especially with psychomotor agitation due to the possibility of worsening anxiety, panic, hallucinations and delusions, as well as in patients who are prone to allergic reactions to drugs of nootropic pyrrolidone. When excessive psycho-emotional exhaustion on the background of chronic stress and fatigue, chronic insomnia, a single dose Fenotropil the first day can cause a sharp need for sleep. Such patients on an outpatient basis should be advised to start taking the drug in exchange holidays. We do not recommend the appointment of Fenotropil children, due to lack of data of the drug in detey.Lekarstvennoe interaction: Fenotropil may exacerbate the effects of drugs that stimulate the central nervous system, antidepressants and nootropics. Fenotropil showing antagonism cataleptic action of neuroleptics, as well as reduces the severity of hypnotic action of ethanol and hexenal. Storage: List B. In dry place protected from light at temperatures above 30 ° C Shelf life 5 years. Do not use after expiry date. Conditions of supply from the pharmacy - a doctor's prescription.
...
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Old 07-18-2012, 09:29 AM #6
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Originally Posted by Death_Taco View Post
Is it hard to get or something?
Very. Antaeus will not be doing another run. Some quotes from users:

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phenylpiracetam is a completely different animal
Quote:
Oh thank goodness. In the midst of non-compliant ingredients making their way into supplements lately [e.g. methylsynephrine, isopropyloctopamine, ostarine, ect.], it's about time someone had the balls to attempt something with one of my favorite compounds. Combined with a stimulant, this stuff puts every preworkout I've ever tried to shame.

Quote:
The other racetams are not even in the same category in terms of the percieved physiological/ergogenic effects.

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Its non-compliant, and for good reason too. I'm friggin unstoppable on that stuff.

Quote:
With phenotropil you'll know if it's a legit source or not, as the effects are not easily duplicated [but you'd still have to purchase first though]. Nonetheless, phenotropil is always available overseas --> just too damn expensive.
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Old 07-18-2012, 09:33 AM #7
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Proven Purity and Jake announces this is the first and last batch.

http://antaeuslabs.blogspot.co.uk/20...-analysis.html
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Old 07-18-2012, 09:47 AM #8
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Old 07-18-2012, 09:56 AM #9
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Old 07-18-2012, 11:22 AM #10
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So ONE guy makes this stuff or what? Don't really have time to research it at the moment.
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Old 07-18-2012, 11:49 AM #11
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Old 07-18-2012, 11:53 AM #12
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Originally Posted by Death_Taco View Post
So ONE guy makes this stuff or what? Don't really have time to research it at the moment.
No, its Antaeus Labs, very reputable company and they provide lab tests in regards to purity on every product they produce.
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Old 07-19-2012, 11:56 AM #13
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Limit doses.
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Old 07-19-2012, 12:55 PM #14
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Originally Posted by Diesel0022 View Post
In regards to dendramine, is there any data showing it does anything good at all?
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Originally Posted by Sldge View Post
protect the retina and improve eye sight.

Unless we wanted more pea hcl but didnt want more dendrobex.
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Originally Posted by Diesel0022 View Post
I couldn't find a single use other then that one of those dilates blood vessels but in turn causues convulsions and is a taurine and beta alanine antagonist.

No hate, just curiosity.
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Originally Posted by Sldge View Post
"Dendrobium alkaloids have protective effects against neuronal damage and we confirmed the hypothesis in the present study. This is one of the first studies to investigate the effects of Dendrobium alkaloids on neuronal damage in the presence of OGD/RP. The system of cortical neuron cultures subjected to OGD/RP was used as a model of ischemic cerebrovascular disease, as described previously (Gifford et al., 1993), Dendrobium alkaloids were administrated at different concentrations in order to evaluate the protective role of Dendrobium alkaloids in OGD/RP damaged neurons."

The convulsions were from high doses of pure dendramine IIRC.
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That study was performed on rats with oxygen-glucose deprivation and reperfusion. Induced damage essentially. Is there any data backing its effects on healthy users in vivo?
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I dont believe dendramine has been studied alone in humans. In the dendramine study you are talking about with regards to convulsions, what was the dose used and what was it studied in?
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Rats and rabbits iirc, hold on, updating as I find it, Yea, here it is. Very high dose.

So since neither directly attribute to healthy human consumption, is it a safe assumption that there is no proof it actually has any benefit for the formula?
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That study is about dendrobine not dendramine.
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Originally Posted by Diesel0022 View Post
Bingo. Because there are none, so, is it a safe assumption that there is no proof it actually has any benefit for the formula?

Also. if you would like to play that game, the abstract you referenced never stated which alkaloids proposed such benefits. As I also doubt it was the 4th and 5th alkaloid as we have established there are no current studies supporting or negating their usage or benefits. So it tends to go in the scrap pile just as mine has been tossed.
...
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Old 07-19-2012, 01:31 PM #15
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Old 07-19-2012, 01:38 PM #16
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Old 07-19-2012, 01:50 PM #17
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I was more poking fun at the lack of comments
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Old 07-19-2012, 02:15 PM #18
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I'll gladly use this as my personal journal haha, makes it easier than bookmarking every damn thing I want to remember.

Strong avoidance of proof.

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Originally Posted by NO HYPE View Post
Well if you have literature that proves PEA is native to dendrobium, then why are you being so secretive about it? Why not present it? You're not protecting any 'proprietary' information, as PEA is a common compound & readily available, so what gives?
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Originally Posted by Sldge View Post
It does add up, you just dont like the answer. Im not releasing it. Go find it for yourself.

Thats hysterical. You must think that these types of documents would only have 5 words on it, "PEA is found in Dendrobium."
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James Neal-Kababick, director of Flora Research Laboratories, told NutraIngredients-USA that much of the work that his lab is doing on dendrobium is “literally unfolding now and it has involved no less than six instrumental techniques and there is much more to do”. Despite his extensive research and use of numerous analytical techniques, Kababick said he is yet to find that phenylethylamines are native to dendrobium.

He could not comment specifically on Craze, but he did say that he is testing several dendrobium extract materials and cut/dried stem pieces. Speaking on the wider issue of dendrobium, he said that his company routinely sees samples that are authentic by HPTLC (high performance thin layer chromatography). “That is, the phytochemicals extracted and profiled match up to authentic dendrobium reference materials. The same goes for many citrus extracts.“However, dendrobium extracts can contain other compounds like beta-phenethylamines. As with steroids and PDE-5 inhibitors, there are almost an unlimited number of analogues that can be created to elude detection.
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Old 07-19-2012, 02:30 PM #19
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Simple reductive logic insists that if the product didn't work, it wouldn't sell. Words are weighed on results.



It's not scientifically feasible to isolate variables so meticulously. We conducted our product development in a controlled environment with safety and performance enhancement in mind. We've tried hundreds of extracts from hundreds of different plants, and we didn't release Craze until we found something extraordinary.
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Originally Posted by Diesel0022 View Post
That was in regards to dendramine alone, where as there is no proof of any positive effects.

And the study posted about "dendramine having positive effects on retinas and improving eyesight" was disproven, the study stated "alkaloids", not once was it specified which alkaloids from Dendrobium.

So right now we are running off.......assumptions?

No disrespect to Matt, or you Andy, these are just questions Ive had bottled up for a while.
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No disrespect taken, but it seems your only satisfaction grounds itself in clinical research that doesn't exist.
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Originally Posted by Diesel0022 View Post
The same place your proof does.
...
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Old 07-19-2012, 05:57 PM #20
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i think you should also have a translation for some of these as it looks like ancient hieroglyphics to me
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Old 07-20-2012, 08:14 AM #21
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