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Piracetam has exhibited many promising attributes in the treatment of cognitive impairment in the elderly and has improved IQ test performance in the healthy middle aged. It has reduced cognitive impairment in healthy individuals resulting from hypoxia (oxygen deprivation) and in animals has dimished cognitive impairment resulting from exposure to a variety of toxic substances, including reduction in neuron degeneration resulting from alcohol abuse and withdrawal. It has been used to variable efficacy in the treatment of dyslexia, dementia (including Alzhiemer's disease), and cortical myoclonus. It seems to positively modulate EEG readings in moderate doses and has virtually no toxicity (unkown LD50). We do not believe piracetam is an all-ecompassing wonderdrug, or something to that effect. It does, however, posses a multitude of unqiue pharmacological properties which lend it to significantly deepening our understanding of cognitive processes. Its lack of toxicity and unique mechanisms of action, in the subtle and indirect modulation of a number of neurotransmitter systems, allude to the necessity to analzye the brain and functional processes on a more holistic level than is normally undertaken with pharmaceutical drugs such as prozac (widely used antidepressant), Adderall (amphetamine derivative used for ADD/ADHD treatment), or benzodiazepine drugs (antiepileptics, anxiolytics). Given advances in pharmacology, neurobiology, and gerontology, it is our belief that over a long timeframe these disciplines have the capacity to significantly fine-tune the imperfect cognitive "wet-ware" that evolution has bestowed upon us. Ubiquitus persecription-dispensing and the giant antidepressant industry highlight on a sociologic scale the necessity to more adequately understand integrative cognitive processes. Understanding the mechanisms of action of unique pharmaceuticals such as piracetam, and further characterizing their cognitive, psychological, and sociologic effects will forward the forementioned understanding of integrative or holistic cognitive processing and also our ability to correct and improve it. This in turn could lead to improvements in psychological health, mental longevity, and productivity. We regress below into a research analysis of piracetam :) Toxicity Piracetam seems to be one of the most non-toxic pharmaceutics ever investigated. In attempted to ascertain its LD50, or dosage at which half of the animals it is adminstered to die, at 8 grams per kg bodyweight piracetam failed to acheive LD50 in being intravenously adminstered to rats. Oral administration to mice, rats, and dogs produced no LD50 at 10g/kg bodyweight. This is equivalent to a 154 pound person taking 1.54 pounds of piracetam. No teratogenic (birth deformity) effects or behavioral tolerance has been evidenced. (1) Piracetam has been used clinically for 25 years and has been well tolerated in doses up to 24g/day in patients treated for cortical myoclonus (involuntary muscle contractions resulting form disorder of controlling motor neurons). (2) Piracetam does not exhibit affinity for a plethora of receptors commonly associated with psychoactivity (serotonin, dopamine, GABA, alpha 1/alpha 2/beta-muscarinic, adenosine A1, mu-opiate, benzodiazepine, and glutamate). (3) Piracetam exhibits virtually no toxicity. sources Dementia In high doses piracetam has been found in some clinical trials to improve cognition in dementia (ie. Alzheimer's) patients (4,5). These data are inconsistent with repeated trials. (6,7) This could be due do variable dosage, adjunct choline supplementation, patient pool characteristics, or other unknown factors. Although inconsistent, piracetam's clinical history seems to support that it does have some efficacy in at least attenuating cognitive deterioration in dementia patients. sources Alcohol-Induced Pathology Piracetam could play a significant role in alleviating pathology and cognitive degeneration associated with alcoholism and alcohol-withdrawal. In animal tests piracetam has attenuated alcohol induced damage incurred during the withdrawal period. (8,9,10) Lipofuscin, a pigment found in increased concentrations as one ages, is found in higher concentrations in the brain with increased alcohol consumption. The catalysis of neural lipofuscin formation found accompanying alcoholism is significantly reduced by piracetam treatment. (11) Alcohol withdrawal is accompanied by significant neuron degeneration, and this degeneration is impeded in animal trials with the administration of piracetam during the withdrawal period. (12) Additionally, preliminary clinical trials with piracetam and alcoholics going through the withdrawal period seems to indicate that the neuroprotective effects evidenced in the animal experiments might be analogously manifest in humans, given improvement in concentration and acheivement tests for piracetam-treated alcoholics going through withdrawal. (13) sources Modulation of Brain Wave State (EEG) Piracetam seems to significantly and selectively potentiate EEG readings in the alpha range in both animals and humans (15,16,17). This is interpreted as a good thing, as alpha waves decrease with decreased oxygen supply (and therefore also with vigilance) and also generally as one ages. (15) Global decrease in EEG activity was induced with single doses of piracetam in healthy volunteers. As dosage was increased (from 2.4g to 9.6g) EEG activity simultaneously increased with dosage until equivalent with placebo. (18) This piracetam-induced decrease in EEG activity is interpreted as an "increased cooperativity of brain functional processes." (19) sources Dyslexia Although piracetam's specific efficacy in treatment of dyslexia is fairly ambiguous at present, it can be inferred that it has at least some efficacy in improving reading rate. In some placebo-controlled experiments with dyslexic children, the piracetam group has exhibited significant improvement over placebo. (24,25) Yet analogous experiments have failed to replicate these results. (26,27) Piracetam does, however, seem to consistently improve reading rates (27,28), and this might play a role in piracetam's apparent efficacy in improving dyslexic pathology. Therefore, even though piracetam does show promise in being a possible effective treatment for dyslexia, its inconsistency in yielding such positive results necessitates further trials before it can be validated in being clinically efficacious for the specific treatment of dyslexia. sources Information Flow Across Corpus Callosum Piracetam increases the flow of information across the corpus callosum, which separates the two hemispheres of the brain. This is evident in increased amplitude of transcallosal evoked potential. (29,30,31) In musicians, the antior half of the corpus callosum is larger than in controls, and information flows across the corpus callosum more readily than in controls. This is experimentally seen using transcranial magnetic stimulation to infer interhemispheric inhibition. (32) sources Chemistry
Toxicity 1. http://www.smart-drugs.net/ias-piracetam.htm citing: -Gouliaev, A. & Senning, A, (1994) "Piracetam and other structurally related nootropics" Brain Res Rev 19, 180-222. -Tacconi, M. & Wurtman, R. (1986) "Piracetam: physiological disposition and mechanism of action" in Advances in Neurology, vol. 43 S. Fahn et al, ed. Raven Press: NY. 2. De Reuck J, Van Vleymen B. The clinical safety of high-dose piracetam--its use in the treatment of acute stroke. Pharmacopsychiatry. 1999 Mar;32 Suppl 1:33-7. 3. Gouliaev AH, Senning A. Piracetam and other structurally related nootropics. Brain Res Brain Res Rev. 1994 May;19(2):180-222. Dementia 4. Enhacement of cognitive abilities beyond placebo was manifest in treatment of 84 geriatric patients exhibiting non-vascular senile cognitive degeneration. Smart Drugs II citing a study by Fioravanti et. al. 5. In a retrospective study of 510 patients with Alzheimer's disease piracetam was found to be comparable in efficacy to acetylcholinesterase inhibitors. Tsolaki M, Pantazi T, Kazis A. Related Articles Efficacy of acetylcholinesterase inhibitors versus nootropics in Alzheimer's disease: a retrospective, longitudinal study. J Int Med Res. 2001 Jan-Feb;29(1):28-36. 6. Review of nootropics in dementia treatment. Nicholson CD. Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharmacology (Berl). 1990;101(2):147-59. 7. http://www.ds-health.com/pir_res.htm#demen (secondary source, excellent experimental references) Alcohol-induced Pathology 8. Piracetam effective in reducing alcohol-induced damage in rats. Sidorov PI, Gromova LE, Solov'ev AG, Degteva GN, Leont'ev VIa, Savastenko AE. [The functional-morphological characteristics of alcohol-induced pathology as dependent on the nature of the intoxication and its nootropil correction in an experiment] Patol Fiziol Eksp Ter. 2000 Jul-Sep;(3):17-9. Russian. 9. Number of synapses in rats undergoing alcohol withdrawal higher when treated with piracetam during withdrawal period. Thought to be due to a protective effect on glutamatergic receptors. Brandao F, Cadete-Leite A, Andrade JP, Madeira MD, Paula-Barbosa MM. "Piracetam promotes mossy fiber synaptic reorganization in rats withdrawn from alcohol." Alcohol. 1996 May-Jun;13(3):239-49. 10. Rats were fed alcohol for 6 months and the experimental group piracetam during the withdrawal period. "no significant differences in the density of the ChAT-IR hippocampal fiber network" were found between the piracetam/control group although "the number of ChAT-IR interneurons in the hippocampal formation was higher" in the piracetam group. piracetam did not have "an effect upon the extrinsic cholinergic innervation", but have "a beneficial effect upon the hippocampal intrinsic cholinergic system." Brandao F, Ribeiro-da-Silva A, Cadete-Leite A. Related Articles GM1 and piracetam do not revert the alcohol-induced depletion of cholinergic fibers in the hippocampal formation of the rat. Alcohol. 1999 Aug;19(1):65-74. 11. lipofuscin formation potentiated by chronic alcohol consumption, withdrawal not reversing changes. piracetam found to decrease formation of neuronal lipofuscin. possibly protective effect on interneuronal membranous system, or antioxidant activity. Paula-Barbosa MM, Brandao F, Pinho MC, Andrade JP, Madeira MD, Cadete-Leite A. The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. Alcohol Clin Exp Res. 1991 Oct;15(5):834-8. 12. Piracetam treatment impedes neuronal degeneration that occurs during alcohol withdrawal. Animals treated with piracetam during withdrawal period exhibited less cell death in hippocampal regions. Brandao F, Paula-Barbosa MM, Cadete-Leite A. "Piracetam impedes hippocampal neuronal loss during withdrawal after chronic alcohol intake." Alcohol. 1995 May-Jun;12(3):279-88. 13. 36 male alcoholics in mild predelirial state studied with series of psychometric tests revealed high probability of having serious cerebral lesions. Piracetam adminstered to 18 of the 36 (9g/day intravenously) improved acheivement and concentration tests, while only slight improvement was seen in other tests. Meyer JG, Forst R, Meyer-Wahl L. "[Course of alcoholic predelirium during treatment with piracetam: results of serial psychometric tests (author's transl)]" Dtsch Med Wochenschr. 1979 Jun 22;104(25):911-4. German. 14. Chronic alcohol consumption and withdrawal affects both excitatory and inhibitory neurons in dentate gyrus. Piracetam may have useful protective role in this condition. Cadete-Leite A, Brandao F, Andrade JP, Ribeiro-da-Silva A, Paula-Barbosa MM. The GABAergic system of the dentate gyrus after withdrawal from chronic alcohol consumption: effects of intracerebral grafting and putative neuroprotective agents. Alcohol Alcohol. 1997 Jul-Aug;32(4):471-84. EEG Modulation 15. Alpha states decrease with aging and nootropics allegedly reverse this. Piracetam (along with the other nootropics) induced increased alpha activity particularly in range above 9.5 Hz with an associated decrease of slow and fast activity in healthy young volunteers. Kinoshita T. "[Quantitative pharmaco-EEG study of nootropics]" Seishin Shinkeigaku Zasshi. 1990;92(5):255-76. Japanese. 16. piracetam enchanced EEG in 10.4-16.4 Hz in 10-40min and above 50min w/electrodes implanted into rat somatosensory cortex, hippocampus and a cannula in the lateral ventricle at a dose of 400mg/kg. glutamatergic component of piracetam's effect focused on. Kovalev GI, Vorob'ev VV, Akhmetova ER, Shibaev NV. "[A phase study of the glutamate-dependent EEG effects in the alpha- and beta-frequency ranges during the acute and subchronic administration of piracetam to rats]" Eksp Klin Farmakol. 2000 Jan-Feb;63(1):3-6. Russian. 17. Piracetam attenuated hypoxia-induced decreases in alpha activity in a double-blind placebo-controlled study with 18 healthy volunteers. Hypoxia increased total EEG with augmentation of delta/theta and decreased alpha activity, the decreased alpha indicating vigilance deterioration. 12g iv and orally induced attenuation in decreased alpha activity. Saletu B, Hitzenberger G, Grunberger J, Anderer P, Zyhlarz G, Linzmayer L, Rameis H. Double-blind, placebo-controlled, pharmacokinetic and -dynamic studies with 2 new formulations of piracetam (infusion and sirup) under hypoxia in man. Int J Clin Pharmacol Ther. 1995 May;33(5):249-62. 18. Global EEG state measured in 12 young healthy volunteers with 2.4, 4.8, 9.6g piracetam and placebo. 1-1.5 hrs after ingestion, EEG complexity decrease was exhibited in the 2.4g group and global complexity returned to placebo values at 9.6g piracetam. The decreased EEG complexity is interpreted as an "increased cooperativity of brain functional processes" and the return to placebo EEG state at high doses illustrates piracetam's U-shaped dose-response curve. Kondakor I, Michel CM, Wackermann J, Koenig T, Tanaka H, Peuvot J, Lehmann D. Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG. Int J Psychophysiol. 1999 Oct;34(1):81-7. 19. 6 subjects under EEG evaluation were requested to press a button after three consecutive or odd digits appeared on a screen, as they were presented in pseudorandom order. 42-channel event-related EEG potential maps (ERP) were obtained for the subjects' states after consecutive digits were displayed. Different landscapes of maps after consecutive digits was interpreted as different configurations of activated neural populations, reflecting different function brain microstates. 19 salient time segments were found in isolating these microstates. Piracetam was administered in 2.9, 4.8, and 9.6g and its influence on the ERP map landscapes was investigated with placebo control. Piracetam mainly affected map landscape of time segments following a triplet's last digit, with a U-shaped dose-response curve (strongest at 4.8g). Suggested that findings indicate that 'single medium piracetam doses selectively activated differently or oriented neurons during cognitive steps of information processing.' Michel CM, Lehmann D. Single doses of piracetam affect 42-channel event-related potential microstate maps in a cognitive paradigm. Neuropsychobiology. 1993;28(4):212-21. 20. Piracetam produced in rats a dose-dependent increase in hippocampal theta rhythm amplitude by stimulation of the brainstem reticular formation. Muscarinic receptor agonist scopolamine reversed these increases, suggesting a common final cholinergic action. Kinney GG, Patino P, Mermet-Bouvier Y, Starrett JE Jr, Gribkoff VK. Cognition-enhancing drugs increase stimulated hippocampal theta rhythm amplitude in the urethane-anesthetized rat. J Pharmacol Exp Ther. 1999 Oct;291(1):99-106. 21. EEG and clinical effects of piracetam evaluated in 24 post-stroke aphasia (deficit in language-comprehension) in double-blind placebo-controlled study. EEG at rest studied before and after 6-week treatment period. Piracetam group exhibited shift in alpha-rhythm from frontal to occipital regions, and this "may be due to a restitution of corticothalamic circuits involved in generation of alpha-activity" Neuropsychological scores were recorded to be more significantly improved in various domains of speech for the piracetam group over the placebo group. Szelies B, Mielke R, Kessler J, Heiss WD. Restitution of alpha-topography by piracetam in post-stroke aphasia. Int J Clin Pharmacol Ther. 2001 Apr;39(4):152-7. 22. http://www.smc.maricopa.edu/academics/revie/bio201/201CH15.htm 23. http://www.brown.edu/Departments/Clinical_Neurosciences/louis/eegfreq.html Dyslexia 24. In a controlled experiment with 60 dyslexic boys aged 8-14, piracetam induced significant improvement in treatment group over the control group. Helfgott E, Rudel RG, Kairam R. The effect of piracetam on short- and long-term verbal retrieval in dyslexic boys. Int J Psychophysiol. 1986 May;4(1):53-61. 25. In treatment of dyslexic children with 3.3g/day piracetam in a placebo-controlled study resulted in the piracetam group doing signifcantly better than placebo. Deberdt W. Interaction between psychological and pharmacological treatment in cognitive impairment. Life Sci. 1994;55(25-26):2057-66. 26. In a blind placebo-controlled study with 60 dyslexic children, piracetam did not "significantly" improve word recognition above controls. Ackerman PT, Dykman RA, Holloway C, Paal NP, Gocio MY. A trial of piracetam in two subgroups of students with dyslexia enrolled in summer tutoring. J Learn Disabil. 1991 Nov;24(9):542-9. 27. In a double-blind, placebo-controlled study with 55 dyslexic boys aged 8-13 years piracetam was adminstered for 12 weeks at 3.3g/daily to the experimental group. Compared to the control group, the piracetam group did not show significant relative improvement in a variety of tests, although reading speed and number of words written in a given time period were enhanced significantly in the piracetam group compared to placebo. Tallal P, Chase C, Russell G, Schmitt RL. "Evaluation of the efficacy of piracetam in treating information processing, reading and writing disorders in dyslexic children." Int J Psychophysiol. 1986 May;4(1):41-52. 28. Dyslexic children treated with piracetam in a placebo-controlled study showed improvements in reading rate. Di Ianni M, Wilsher CR, Blank MS, Conners CK, Chase CH, Funkenstein HH, Helfgott E, Holmes JM, Lougee L, Maletta GJ, et al. "The effects of piracetam in children with dyslexia." J Clin Psychopharmacol. 1985 Oct;5(5):272-8. Information Flow Across Corpus Callosum 29. piracetam increases amplitude of primary transcallosal evoked potential, and increases rise and stabilization of predominant peak in distribution of EEG power spectrum that corresponds to improvement of theta rhythm organization. Krapivin SV, Voronina TA. "[Comparative neurophysiological study of the nootropic drugs piracetam and centrophenoxine]" Farmakol Toksikol. 1987 Nov-Dec;50(6):17-20. Russian. 30. piracetam dose-dependently enhanced the amplitudes of trancallosal responses Kirsch U, Schmidt J. "[Facilitation of evoked transcallosal responses by nootropic agents]" Biomed Biochim Acta. 1985;44(4):631-6. German. 31. piracetam catalyzed one-eyed pattern discrimination and "enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning." Buresova O, Bures J. "Piracetam-induced facilitation of interhemispheric transfer of visual information in rats." Psychopharmacology (Berl). 1976;46(1):93-102. 32. antior half of corpus callosum is larger in musicians. transcranial magnetic stimulation in six adult professional musicians and controls revealed that interhemispheric inhibitory circuits activated by TMS are less effect in musicians than in controls Ridding MC, Brouwer B, Nordstrom MA. "Reduced interhemispheric inhibition in musicians." Exp Brain Res. 2000 Jul;133(2):249-53. 33. TEP suggested as potentially helpful in detection of new drugs with nootropic effect Voronina TA, Krapivin SV, Nerobkova LN. "Specificity of the action of piracetam, encephabol and Cleregil on the transcallosal evoked potential] Biull Eksp Biol Med. 1986 Mar;101(3):320-2. Russian. Additional Secondary Sources http://www.nootropics.com/ http://members.aol.com/profchm/piracetam.html http://members.aol.com/TheRagans/fyi.htm http://www.hyperreal.org/nootropics/piracetam http://www.smart-drugs.net/ias-piracetam.htm http://www.biopsychiatry.com http://smart-drugs.net/ias-nootropics.htm http://www.ceri.com/noot.htm http://www.nootrope.net/nootropics.html http://www.ds-health.com/pir_res.htm Contraindications Caffeine, amphetamine, MSG, and other psychotropics might potentiate the effects of piracetam. Alcohol and amphetamine are explicitly contraindicated by the manufacturer. can I get more information on piracetam? -pubmed has many many articles on piracetam collected over the years. it can be accessed from this page: http://www4.ncbi.nlm.nih.gov/PubMed/ type in piracetam and check out the articles -two books, Smart Drugs I and II, have been published by reputable doctors and contain a whole lot of information on piracetam and many other nootropics. exerpts from these books are ubiquitus on the net when one is searching for piracetam -throw piracetam into google or hotbot |
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Brain Res Brain Res Rev 1994 May;19(2):180-222 Gouliaev AH, Senning A. Department of Chemistry, Aarhus University, Denmark.
Brain lipofuscinolysis and ceroidolysis--to be or not to be. Gerontology 1995;41 Suppl 2:271-81 Riga D, Riga S. Institute of Neurology and Psychiatry, Bucharest, Romania.
The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. Alcohol Clin Exp Res 1991 Oct;15(5):834-8 Related Articles, Books, LinkOut Paula-Barbosa MM, Brandao F, Pinho MC, Andrade JP, Madeira MD, Cadete-Leite A. Department of Anatomy, Porto Medical School, Portugal.
Learning and memory impairment in albino rats after potassium ethylxanthogenate. Effects of nootropic agents. Acta Physiol Pharmacol Bulg 1991;17(2-3):75-83 Related Articles, Books, LinkOut Genkova-Papasova M, Lazarova-Bakarova M. Institute of Physiology, Bulgarian Academy of Sciences.
Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs. Curr Pharm Des 2002;8(2):125-38 Related Articles, Books, LinkOut Gualtieri F, Manetti D, Romanelli MN, Ghelardini C. Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Via G. Capponi 9, I-50121, Firenze, Italy. fulvio.gualtieri@unifi.it
Piracetam in the treatment of cortical myoclonus Pharmacopsychiatry 1999 Mar; 32 Suppl 1:49-53 Genton P, Guerrini R, Remy C. Centre Saint Paul, Marseille and Department of Neurophysiology, Hopital Pasteur, Nice, France.
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