Posted 29 July 2008 - 08:39 AM



Slow-wave sleep, acetylcholine, and memory consolidation



A slew of really excellent reads follows, starting with a three-part exploration of brain cholinesterase and various theoretical and practical implications:

degeneration

attenuate

long-term

Lot of interest in Huperzine A on here. I've never taken it or thoroughly researched it until now.Here is a lot of research to read (well worth reading) and contemplate and debate. These are all interesting studies, carefully sifted through, with information you probably haven't read before.I hope to increase the complexity of the discussion of Huperzine A on this board.Huperzine A shouldn't be taken blindly and just based off of a few glowing reports on here or on some internet website that sells it.[Uh, this thread isn't for people who don't like to read and think. Those looking for a perky soundbite - move along!]Caution even from those who sell it:Off of Relentless Improvement.Huperzine A (Huperzia serrata) (aerial plant)Dosage and UseTakedaily, or as recommended by a healthcare practitioner..*CautionBecause vitamin E inhibits blood clotting, it should not be used if excessive bleeding is occurring. Since Huperzine A inhibits the enzyme acetylcholinesterase, it should not be used on a chronic basis.While most people over age 30 need more acetylcholine, too much can cause unpleasant side effects.[my edit: Huperzine A is not a precursor]and phosphatidylcholine along with pantothenic acid. The COGNITEX formula contains these acetylcholine precursor agents. Do not take Huperzine A if you are taking other acetylcholinesterase inhibitors like Aricept or Tacrine.INTERACTIONSDRUGSAcetylcholinesterase Inhibitors: Use of huperzine A along with the acetylcholinesterase inhibitors donepezil or tacrine may produce additive effects, including additive adverse effects. Other acetylcholinesterase inhibitors include neostigmine, physostigmine and pyridostigmine, and use of these agents along with huperzine A may produce additive effects, including additive adverse effects.Cholinergic Drugs: Use of huperzine A along with cholinergic drugs, such as bethanechol, may produce additive effects, including additive adverse effects.Because of possible adverse effects in those with seizure disorders, cardiac arrhythmias and asthma, those with these disorders should avoid huperzine A. Those with irritable bowel disease, inflammatory bowel disease and malabsorption syndromes should avoid huperzine A.Warnings:Keep out of reach of children.Do not exceed recommended dose.Do not purchase if outer seal is broken or damaged.If you have a bad reaction to product discontinue use immediately.When using nutritional supplements, please inform your physician if you are undergoing treatment for a medical condition or if you are pregnant or lactating.Off of the LEF site:"Healthy people, on the other hand, need acetylcholinesterase to regulate acetylcholine levels in their brains."."Warnings about pharmaceutical grade versus health store/website Huperzine A:Consider ACh levels (during the day and at night) and memory consolidation:[My comments and questions] If one has a lot of ACh during the day from a choline-donator would the breakdown mechanism (AChE) work harder to break it down and lower ACh levels for during sleep or would they remain high overnight? If one used a cholinesterase inhibitor how high would one's ACh levels chonically be overnight? Huperzine A is described as potent and selective and what concerns me is this line from the recent FDA study below ("Gradual recovery of AChE activity then occurs, but even 48h after the last dose red blood cell AChE was about 10% below control (pre-dose) values."). So, it is long acting and ACh levels are still higher than baseline levels even two days after the dose.Concerning? Or would ACh levels still be higher than baseline two days after dosing with CDP-Choline, say? Anyone know of any studies showing how long the effect of a choline-donor lasts? It is great to have ACh and more working memory, but wouldn't be at all great if what I read and learned during the day wasn't being processed into long-term memory as effectively overnight.LTM is where it is at! Chem Biol Interact. 2008 May 3. [Epub ahead of print] <a href="http://java%20script/;" class="bbc_url" title="External link" rel="nofollow external">Links</a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Aisen%20PS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Aisen PS</strong></a> . Walter Reed Army Institute of Research, Division of Biochemistry, 503 Robert Grant Road, Silver Spring, MD 20910-7500, USA., twelve (12) healthy elderly individuals received an escalating dose regimen of huperzine A (100, 200, 300, and 400mug doses, twice daily for a week at each dose), with three (3) individuals as controls receiving a placebo. Using the WRAIR whole blood cholinesterase assay, red blood cell AChE and plasma butyrylcholinesterase (BChE) were measured in unprocessed whole blood samples from the volunteers following each dose, and then for up to 48h following the final and highest (400mug) dose to monitor the profile of. Significant inhibition of AChE was observed, ranging from 30-40% after 100mug to >50% at 400mug, and peaking 1.5h after the last dose.Huperzine A levels in plasma peaked 1.5h after the final 400mug dose (5.47+/-2.15ng/mL). Plasma BChE was unaffected by huperzine A treatment (as expected). Aliquots of huperzine A-containing (from three individuals) and placebo blood samples were exposed ex vivo to the irreversible nerve agent soman (GD) for 10min, followed by removal of unbound huperzine and soman from the blood by passing through a small C(18) reverse phase spin column. Eluted blood was diluted in buffer, and aliquots taken at various time intervals for AChE and BChE activity measurement to determine the time taken to achieve full return in activity of the free enzyme (dissociation from the active site of AChE by huperzine A), and thus the proportion of AChE that can be protected from soman exposure. Huperzine A-inhibited red blood cell (RBC) AChE activity was restored almost to the level that was initially inhibited by the drug. The increased doses of huperzine A used were well tolerated by these patients and in this ex vivo study sequestered more red blood cell AChE than has been previously demonstrated for pyridostigmine bromide (PB), indicating the potential improved prophylaxis against organophosphate (OP) poisoning.PMID: 18572153 [PubMed - as supplied by publisher]. <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Med Hypotheses.</a> 2004;63(2):285-97. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15236793&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0306987704001677" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Shen%20ZX%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Shen ZX</strong></a> . 2436 Rhode Island Avenue N. #3, Golden Valley, MN 55427-5011, USA. zhengxshen@yahoo.comSubstantial evidence is presented demonstrating that it is the cholinesterases (ChEs) that constituteMultiple classic and/or putative neurotransmitters and neuromodulators, virtually all the peptide hormones of the endocrine and neuroendocrine systems in the brain, their specific synthesizing and hydrolyzing marker enzymes and associated uptake processes (transporters), and receptors, do not actually participate in the formation of senile plaques and neurofibrillary tangles in the brains of patients suffering from AD. The massive perturbation in different neurochemicals seen in AD is essentially. The graded patterns of brain ChEs expression affect the preferential vulnerability and severity of the AD clinico-pathologic presentation. It seems that the common law in nature may also dominate the destiny of brain ChEs system, i.e.,PMID: 15236793 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Med Hypotheses.</a> 2004;63(2):308-21. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15236795&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0306987704001653" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Shen%20ZX%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Shen ZX</strong></a> . 2436 Rhode Island Avenue #3, Golden valley, MN 55427-5011, USA. zhengxshen@yahoo.comCurrently available evidence demonstrates that, owing to their powerful enzymatic and non-catalytic actions, unusually strong electrostatics, andThe widespread intracellular and extracellular membrane networks of ChEs in the brain are also subject to various insults, such as aging, gene anomalies, environmental hazards, head trauma, excessive oxidative stress,The alteration in ChEs on the intracellular compartments membranous network may give rise to the development ofThe abnormal patterns of glycosylation and configuration changes in ChEs may be reflecting their impaired metabolism at the molecular and cellular level and causing thedetected in brain tissue and/or CSF of patients with AD and in specimens in laboratory experiments. The inflammatory reactions mainly arising from ChEs-containing neuroglial cells may facilitate the pathophysiologic process of AD.PMID: 15236795 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Med Hypotheses.</a> 2004;63(2):298-307. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15236794&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0306987704001665" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Shen%20ZX%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Shen ZX</strong></a> . 2436 Rhode Island Ave. N. #3, Golden Valley, MN 55427-5011, USA. zhengxshen@yahoo.comBased on the, treatment should be designed tothe cranial ChEs system from alteration and/or to help that systemthrough restoring its homeostatic action for brain structure and function instead. The overlap in the clinical, biochemical, molecular-cellular, and pathological alterations seen in patients with AD and individuals with many other brain disorders, which has bewildered many investigators, may now be explained by the shared underlying. The abnormal metabolism of ChEs existing in asymptomatic subjects may indicate that the system is "at risk" and deserves serious attention. Future perspectives of ChEs research in vivo and in vitro in connection with AD and clinical diagnosis, prevention and treatment are proposed. Several potentially useful therapeutic and preventive means and pharmacological agents in this regard are identified and discussed, such as physical and intellectual stimulation, and a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline), acetyl L-carnitine, cytidine diphosphocholine (), centrophenoxine, L-phenylalanine, naloxone, galactose, and lithium,PMID: 15236794 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Med Hypotheses.</a> 2008;70(1):43-51. Epub 2007 Jun 22. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17587508&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0306-9877%2807%2900321-0" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Shen%20ZX%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Shen ZX</strong></a> . Zhengxshen@yahoo.comRecent evidence strongly demonstrates that acetylcholine () is not only involved in the function of the central and peripheral nervous systems, including the parasympathetic and somatic systems, but also acts as amolecule or cytotransmitter, and as a hormone with paracrine, juxtacrine and autocrine properties. This active molecule exerts versatile and potent functions primarily through its specific nicotinic and muscarinic receptors (nAChRs and mAChRs, respectively). These functions, including cell growth, survival, proliferation and differentiation, cell-cell contact, cell cycle, locomotion, electrical activity, immune function, apoptosis, organization of the cytoskeleton, trophic functions, secretion, adhesion, resorption, and stress-response-regulation.Once ChEs become critically deficient in quality and quantity, ACh signaling will be uncontrollably aberrant and persistent. An in-depth account of the fundamental roles of ChEs, comprising their diverse soluble and membrane-bound forms, inin the macro and microenvironment has been undertaken. This work also covers ACh receptors, signaling pathways, other interdependent and interrelated substances, functional processes,, in tissues and body fluids in order for conducting clinical diagnosis, prevention and treatment.Evidence is adduced for the safety and efficacy of ChEs treatment.PMID: 17587508 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Int J Neuropsychopharmacol.</a> 2006 Feb;9(1):101-24. Epub 2005 Aug 5. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3288&itool=AbstractPlus-def&uid=16083515&db=pubmed&url=http://journals.cambridge.org/abstract_S1461145705005833" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.cambridge.org-images-cjo.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Enz%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Enz A</strong></a> . Novartis Neuroscience, Novartis Pharmaceuticals Corporation, NJ, USA.Inhibition of brain acetylcholinesterase (AChE) has been the major therapeutic target of ChE-I treatment strategies for Alzheimer's disease (AD). AChE-positive neurons project diffusely to the cortex, modulating cortical processing and responses to new and relevant stimuli. Butyrylcholinesterase (BuChE)-positive neurons project specifically to the frontal cortex, and may have roles in attention, executive function, emotional memory and behaviour. Furthermore, BuChE activity progressively increases as the severity of dementia advances, while. Therefore, inhibition of BuChE may provide additional benefits. The two cholinesterase (ChE) enzymes that metabolize acetylcholine (ACh) differ significantly in substrate specificity, enzyme kinetics, expression and activity in different brain regions, and complexity of gene regulation. In addition,If these additional mechanisms are demonstrated to underlie clinically meaningful effects,that is limited to symptomatic treatment, ignoring the potential of cholinergic therapies to modify the disease process, may be appropriate. The specificity of ChE inhibitory activity, up-regulation of AChE activity and changes in the composition of AChE molecular forms over time, selectivity for AD-relevant ChE molecular forms, brain vs. peripheral selectivity, and pharmacokinetic profile may be important determinants of the acute and long-term efficacy, safety and tolerability profiles of the different ChE-Is. This review focuses onfor the roles of BuChE and AChE in symptom generation and rate of underlying disease progression in dementia, andPMID: 16083515 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Clin Neuropharmacol.</a> 2004 May-Jun;27(3):141-9. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3159&itool=AbstractPlus-def&uid=15190239&db=pubmed&url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0362-5664&volume=27&issue=3&spage=141" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.lwwonline.com-pt-pt-core-template-journal-lwwgateway-images-pmlogo.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Greig%20NH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Greig NH</strong></a> . Novartis Neuroscience, Novartis Pharmaceuticals Corp., East Hanover, NJ 07936-1080, USA. roger.lane@novartis.comTherefore, the use of AChE inhibitors to treat symptoms caused by cholinergic imbalances in Alzheimer disease (AD) represented a rational approach. However, it is now clear that AChE and the cholinergic system may havein AD. Of particular interest may be signal transduction pathways mediated through cholinergic receptors that promote nonamyloidogenic amyloid precursor protein processing and decrease tau phosphorylation, and the role of AChE in the aggregation of beta-amyloid (Abeta) peptide. In addition, the neuronal and nonneuronal cholinergic systems have important roles in the modulation of regional cerebral blood flow. These findings may modify thethat is limited to symptomatic treatment and ignores the potential of cholinergic therapies as disease-modifying agents.whereas, remarkably, irreversible or very slowly reversible ChE-Is do not seem to have this effect. If such differences between ChE-Is are shown to have clinical correlates, this mayPMID: 15190239 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Drugs Aging.</a> 2006;23(6):503-11. <a href="http://java%20script:PopUpMenu2_Set%28Menu16872233%29;" class="bbc_url" title="External link" rel="nofollow external">Links</a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ancoli-Israel%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Ancoli-Israel S</strong></a> . Department of Medicine, University of California, San Diego, California, USA.BACKGROUND AND OBJECTIVE: Studies suggest thatbut few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs. METHODS: 76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed.Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters. CONCLUSION: Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest thatby the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD.PMID: 16872233 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Chem Biol Interact.</a> 2005 Dec 15;157-158:227-32. Epub 2005 Oct 27. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=16256970&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0009-2797%2805%2900276-0" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Vidal%20CJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Vidal CJ</strong></a> . Departamento de Bioquímica y Biología Molecular-A, Edificio de Veterinaria, Universidad de Murcia, Apdo. 4021, E-30071 Murcia, Spain. cevidal@um.esAlthough the involvement of cholinesterases (ChEs) in the removal of acetylcholine (ACh) at cholinergic synapses is firmly established, there isand their role in morphogenesis and apoptosis have been explained on the basis of the non-cholinergic actions of ChEs. In addition, the effects of AChE and BuChE, their inhibitors and antisense oligonucleotides in proliferating cellular systems, together with the mitogenic actions of ACh, support a role for ChEs in cell cycle control.The aim of this report is to compile the available information on ChEs in cancerous tissues in order to stimulating the research to clarify the molecular mechanisms by whichFuture investigations may throw light into this intriguing issue which will be ofPMID: 16256970 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Life Sci.</a> 2003 Mar 28;72(18-19):2055-61. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=12628456&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0024320503000833" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Kirkpatrick%20CJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Kirkpatrick CJ</strong></a> . Institute of Pharmacology, University of Mainz, Obere Zahlbacher Str 67, D-55101 Mainz, Germany. wessler@uni-mainz.deAcetylcholine, a prime example of a neurotransmitter, has been detected in bacteria, algae, protozoa, and primitive plants, indicating an. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase (ChAT), have been found in epithelial cells (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (mononuclear cells, granulocytes, alveolar macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by theand receptors (nicotinic, muscarinic). Thus, the non-neuronal cholinergic system and non-neuronal acetylcholine, acting as a local cellular signaling molecule, has to be discriminated from the neuronal cholinergic system and neuronal acetylcholine, acting as neurotransmitter. In the human placenta anti-ChAT immunoreactivity is found in multiple subcellular compartments like the cell membrane (microvilli, coated pits), endosomes, cytoskeleton, mitochondria and in the cell nucleus. These locations correspond with the results of experiments whereof non-neuronal acetylcholine have been identified (proliferation, differentiation, organization of the cytoskeleton and the cell-cell contact, locomotion, migration, ciliary activity, immune functions). In the human placenta acetylcholine release is mediated by organic cation transporters. Thus, structural and functional differences are evident between the non-neuronal and neuronal cholinergic system.Copyright 2003 Elsevier Science Inc.PMID: 12628456 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">J Pharmacol Sci.</a> 2008 Feb;106(2):167-73. Epub 2008 Feb 16. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3580&itool=AbstractPlus-def&uid=18285657&db=pubmed&url=http://joi.jlc.jst.go.jp/JST.JSTAGE/jphs/FM0070073?from=PubMed" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkout.jstage.jst.go.jp-logo.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Fujii%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Fujii T</strong></a> . Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan. koichiro-jk@piano.ocn.ne.jpAcetylcholine (ACh) is a phylogenetically ancient molecule involved in cell-to-cell signaling in almost all life-forms on earth. Cholinergic components, including ACh, choline acetyltransferase, acetylcholinesterase, and muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively) have been identified in numerous non-neuronal cells and tissues, including keratinocytes,urinary bladder, airway epithelial cells, vascular endothelial cells, and reproductive organs, among many others. Stimulation of the mAChRs and nAChRs elicits cell-specific functional and biochemical effects. These findings support the notion that non-neuronal cholinergic systems are expressed in certain cells and tissues and are involved in the regulation of their function and thatPMID: 18285657 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Br J Pharmacol.</a> 2008 May 26. [Epub ahead of print] <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3094&itool=AbstractPlus-def&uid=18500366&db=pubmed&url=http://dx.doi.org/10.1038/bjp.2008.185" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_npg.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Kirkpatrick%20CJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Kirkpatrick CJ</strong></a> . 1Institute of Pathology, University Hospital, Johannes Gutenberg-University, Mainz, Germany.Animal life is controlled by neurons and in this setting cholinergic neurons play an important role. Cholinergic neurons release ACh, which via nicotinic and muscarinic receptors (n- and mAChRs) mediate chemical neurotransmission, a highly integrative process. Thus, the organism responds to external and internal stimuli to maintain and optimize survival and mood. Blockade of cholinergic neurotransmission is followed by immediate death. However, cholinergic communication has been established from the beginning of life in primitive organisms such as bacteria, algae, protozoa, sponge and primitive plants and fungi, irrespective of neurons. Tubocurarine- and atropine-sensitive effects are observed in plants indicating functional significance. All components of the cholinergic system (ChAT, ACh, n- and mAChRs, high-affinity choline uptake, esterase) have been demonstrated in mammalian non-neuronal cells, including those of humans. Embryonic stem cells (mice), epithelial, endothelial and immune cells synthesize ACh, which via differently expressed patterns of n- and mAChRsto respond to internal or external stimuli. This helps to, such as proliferation, differentiation, formation of a physical barrier, migration, and ion and water movements. Blockade of n- and mACHRs on non-innervated cells causes cellular dysfunction and/or cell death. Thus,Alterations have been detected in inflammatory processes and a pathobiologic role of non-neuronal ACh in different diseases is discussed. The present article reviews recent findings about the non-neuronal cholinergic system in humans.British Journal of Pharmacology advance online publication, 26 May 2008; doi:10.1038/bjp.2008.185.PMID: 18500366 [PubMed - as supplied by publisher] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Curr Alzheimer Res.</a> 2005 Jul;2(3):307-18. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3037&itool=AbstractPlus-def&uid=15974896&db=pubmed&url=http://www.bentham-direct.org/pages/content.php?CAR/2005/00000002/00000003/005AT.SGM" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.bentham-direct.org-images-ben_pubmed_flag1.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Darvesh%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Darvesh S</strong></a> . Department of Biomedical Sciences, Wolfson Centre for Age-related Diseases, Hodgkin Building, Guy's Campus, King's College, London, SE1 1UL, UK. clive.ballard@kcl.ac.ukTheof decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placedalongside AChE as an important contributor to the occurrence, symptoms, progression and responses to treatment in dementia.. Data suggest involvement of the ChEs in modulating glial activation, cerebral blood flow, the amyloid cascade, and tau phosphorylation. It has therefore been speculated that some actions of the ChEs could affect the underlying disease processes in Alzheimer's disease (AD), and that. Focusing on new findings relating to BuChE, we review recent evidence that hasPMID: 15974896 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Neurochem Res.</a> 2003 Apr;28(3-4):515-22. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3055&itool=AbstractPlus-def&uid=12675140&db=pubmed&url=http://www.kluweronline.com/art.pdf?issn=0364-3190&volume=28&page=515" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Giacobini%20E%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Giacobini E</strong></a> . University Hospitals of Geneva, Department of Geriatrics, University of Geneva, Medical school. CH-1226 Thônex, Geneva, Switzerland. Ezio.Giacobini@hcuge.chThe most important therapeutic effect of cholinesterase inhibitors (ChEI) on approximately 50% of Alzheimer's disease (AD) patients is to stabilize cognitive function at a steady level during a 1-year period of treatment as compared to placebo. Recent studies show that in a certain percentage (approximately 20%) of patients this cognitive stabilizing effect can be prolonged up to 24 months. This long-lasting effect suggests a mechanism of action other than symptomatic and cholinergic. In vitro and in vivo studies have consistently demonstrated a link between cholinergic activation and APP metabolism. Lesions of cholinergic nuclei cause a rapid increase in cortical APP and CSF. The effect of such lesions can be reversed by ChEI treatment. Reduction in cholinergic neurotransmission--experimental or pathological, such as in AD--leads to amyloidogenic metabolism and contributes to the neuropathology and cognitive dysfunction. To explain the long-term effect of ChEI, mechanisms based on beta-amyloid metabolism are postulated. Recent data show that this mechanism may not necessarily be related to cholinesterase inhibition. A second important aspect of brain cholinesterase function is related to enzymatic differences. The brain of mammals contains two major forms of cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The two forms differ genetically, structurally, and for their kinetics. Butyrylcholine is not a physiological substrate in mammalian brain, which makes the function of BuChE of difficult interpretation. In human brain, BuChE is found in neurons and glial cells, as well as in neuritic plaques and tangles in AD patients. Whereas, AChE activity decreases progressively in the brain of AD patients, BuChE activity shows some increase. To study the function of BuChE, we perfused intracortically the rat brain with a selective BuChE inhibitor and found that extracellular acetylcholine increased 15-fold from 5 nM to 75 nM concentrations with little cholinergic side effect in the animal. Based on these data and on clinical data showing a relation between cerebrospinal fluid (CSF) BuChE inhibition and cognitive function in AD patients, we postulated that two pools of cholinesterases may be present in brain, the first mainly neuronal and AChE dependent and the second mainly glial and BuChE dependent. The two pools show different kinetic properties with regard to regulation of ACh concentration in brain and can be separated with selective inhibitors. Within particular conditions, such as in mice nullizygote for AChE or in AD patients at advanced stages of the disease, BuChE may replace AChE in hydrolizing brain acetylcholine.PMID: 12675140 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Mech Ageing Dev.</a> 2001 Nov;122(16):2025-40. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11589920&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0047637401003104" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Wallin%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Wallin A</strong></a> . Clinical Research Unit, Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Via Scalzino 3, 62032, Camerino, Italy. amenta@cambio.unicam.itThe observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition. Inhibition of endogenous ACh degradation through ChE inhibitors and precursor loading were treatments more largely investigated in clinical trials. Of the numerous compounds in development for the treatment of AD, AChE and ChE inhibitors are the most clinically advanced, although clinical trials conducted to date did not always confirm a significant benefit of these drugs on all symptom domains of AD. The first attempts in the treatment of AD with cholinergic precursors did not confirm a clinical utility of this class of compounds in well controlled clinical trials. However, cholinergic precursors most largely used such as choline and phosphatidylcholine (lecithin) were probably not suitable for enhancing brain levels of ACh. Other phospholipids involved in choline biosynthetic pathways such as CDP-choline, choline alphoscerate and phosphatidylserine clearly enhanced ACh availability or release and provided a modest improvement of cognitive dysfunction in AD, these effects being more pronounced with choline alphoscerate. Although some positive results cannot be generalized due to the small numbers of patients studied, they probably would justify reconsideration of the most promising molecules in larger carefully controlled trials.PMID: 11589920 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Curr Med Chem.</a> 2008;15(5):488-98. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3037&itool=AbstractPlus-def&uid=18289004&db=pubmed&url=http://www.bentham-direct.org/pages/content.php?CMC/2008/00000015/00000005/0008C.SGM" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.bentham-direct.org-images-ben_pubmed_flag1.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Tayebati%20SK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Tayebati SK</strong></a> . Dipartimento di Medicina Sperimentale e Sanità Pubblica, Università di Camerino, 62032 Camerino, Italy. francesco.amenta@unicam.itAcetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.PMID: 18289004 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Crit Rev Neurobiol.</a> 2005;17(3-4):161-217. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=4847&itool=AbstractPlus-def&uid=17341198&db=pubmed&url=http://www.begellhouse.com/journals/7b004699754c9fe6,0c6ebf4a55da92b6,7f45271578c3b24d.html" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.begellhouse.com-i-full_logo_begell.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Phillis%20JW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Phillis JW</strong></a> . Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA. jphillis@med.wayne.eduSome 50 years have elapsed since Elliot et al. and MacIntosh & Oborin first reported a release of acetylcholine (ACh) from canine and feline cerebral cortices, respectively. In this review, subsequent developments in the field during the succeeding five decades are explored. The arrangement of material in the review is outlined in this abstract, concluding with some suggestions as to its potential significance. A number of technical advances during this period have contributed to a greater understanding of the role that ACh may play in the central nervous system. These include the relatively recent evolution of the microdialysis and transverse dialysis techniques that enabled investigators to explore ACh release in deep regions of the brain. Future studies will likely be refined with the use of microelectrode biosensors, which should allow real-time measurements of ACh concentrations at the synaptic level. Controversies arising from the use of cholinesterase inhibitors and muscarinic receptor antagonists to enhance release are being resolved as a result of a better understanding of the presynaptic actions of these agents. Future studies will also benefit from the recent development of clostridial and other neurotoxins to reduce ACh release in areas of the brain. The likelihood that ACh may act as a cotransmitter at synapses in conjunction with glutamic acid, nitric oxide, and adenosine triphosphate is also explored. Attention is focused on the elucidation of choline acetyl-transferase (ChAT)-containing pathways in the central nervous system using techniques such as immunohistochemistry, in situ hybridization, histochemistry of ChAT mRNA, acetylcholinesterase histochemistry, and the distribution of the vesicular ACh transporter. Such studies have defined several major groupings of cholinergic neurons in the brain, which provide ascending or descending projections to higher and lower central structures. A major section of the review is devoted to actual studies on ACh release in the brain and spinal cord. This presentation is in two sections. The text details some of the material that has been obtained in experiments over the past 50 years. In five Tables, the results obtained in the majority of release studies to date are summarized. Although the data obtained to date clearly support the hypothesis that ACh is involved in electroencephalographic activation associated with cerebral cortical arousal, this occurs while the animals appear to be awake with full postural control, suggesting that noncholinergic pathways to the cerebral cortex are also involved in such behavioral manifestations. The roles of acetylcholine in cognitive processes such as attention, learning, memory, responses to environmental changes, and motor activity still remain to be defined.PMID: 17341198 [PubMed - indexed for MEDLINE] <a href="http://java%20script:AL_get%28this,%20" class="bbc_url" title="External link" rel="nofollow external">Methods Find Exp Clin Pharmacol.</a> 2006 Sep;28 Suppl B:1-56. <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3024&itool=AbstractPlus-def&uid=17171187&db=pubmed&url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=3400" class="bbc_url" title="External link" rel="nofollow external"><span rel="lightbox"><img class="bbc_img" src="http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.prous.com-icons-prous.gif" alt="Posted Image"></span></a> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lorenzo%20JL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" class="bbc_url" title="External link" rel="nofollow external"><strong class="bbc">Lorenzo JL</strong></a> . Medical Department, Grupo Ferrer S.A., Barcelona, Spain.Cytidine 5'-diphosphocholine, CDP-choline, or citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Following administration by both the oral and parenteral routes, citicoline releases its two main components, cytidine and choline. Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. These pharmacological characteristics and the action mechanisms of citicoline suggest that this product may be indicated for treatment of cerebral vascular disease, head trauma (HT) of varying severity, and cognitive disorders of different causes. In studies conducted in the treatment of patients with HT, citicoline was able to accelerate recovery from post-traumatic coma and neurological deficits, achieving an improved final functional outcome, and to shorten hospital stay in these patients. Citicoline also improved the mnesic and cognitive disorders seen after HT of minor severity that constitute the so-called post-concussional syndrome. In the treatment of patients with acute ischemic cerebral vascular disease, citicoline accelerates recovery of consciousness and motor deficit, achieves a better final outcome, and facilitates rehabilitation of these patients. The other major indication of citicoline is for treatment of senile cognitive impairment, either secondary to degenerative diseases (e.g. Alzheimer disease) or to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, citicoline improves scores in cognitive rating scales, while in patients with senile dementia of the Alzheimer type it stops the course of disease, and neuroendocrine, neuroimmunomodulatory, and neurophysiological benefits have been reported. Citicoline has also been shown to be effective in Parkinson disease, drug addictions, and alcoholism, as well as in amblyopia and glaucoma. No serious side effects have occurred in any series of patients treated with citicoline, which attests to the safety of treatment with citicoline. © 2006 Prous Science. All rights reserved.PMID: 17171187 [PubMed - indexed for MEDLINE]

Edited by Rags847, 29 July 2008 - 09:35 AM.