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> CDP-Choline (Citicoline) Research, From A-Z
LifeMirage
post Apr 07, 2006, 05:47 PM
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CDP-Choline In Age-Related Mental Decline

Rev Neurol 2002 Oct 1;35(7):675-82
Treatment of mild cognitive impairment: value of citicoline


Abad Santos F, Novalbos J, Gallego Sandin S, Garcia AG. Hospital Universitario de la Princesa, Madrid, Espa a.

AIMS. The course of mild cognitive impairment (MCI) involves a slight loss of memory without any significant effects on other cognitive functions. Around 12% of these patients advance annually toward Alzheimer s disease, and for this reason it is important to search for medications that can prevent or slow down the evolution to dementia. Memory training programs, with relaxation techniques, the repetition of facts, information or pictures, categorizing information and the use of mnemonic rules can be effective. Drugs that can improve the cognitive faculties include piracetam, selegiline, vitamin E, Ginkgo biloba extract, estrogens, nonsteroidal antiinflammatory drugs (NSAIDs), acetylcholinesterase inhibitors and memantine. The aim of this study is to evaluate whether citilcoline can be effective in this clinical situation. METHOD. It has been shown in several animal models that citicoline improves scoring in learning and memory tests. Likewise, citicoline has been shown to improve memory and other cognitive functions in patients with chronic cerebrovascular disease or dementia and in old people suffering from memory deficit without dementia. Furthermore, a meta analysis of 12 clinical trials conducted by the Cochrane Collaboration, researchers reached the conclusion that citicoline improves memory, behaviour and the overall clinical impression in old people suffering from chronic brain diseases. CONCLUSION. Citicoline could be effective in the treatment of MCI, although more studies are needed in order to check whether the effect continues in the long term and whether it manages to slow down the progression to dementia.


Psychopharmacology (Berl) 2002 May;161(3):248-54
Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study.


Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Consolidated Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA,

RATIONALE: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. OBJECTIVES: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy ((31)P-MRS) before and after citicoline treatment. METHODS: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a (31)P-MRS scan at baseline and following 6 and 12 weeks of treatment. RESULTS: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters ( P=0.008), including an 11.6% increase in glycerophosphoethanolamine ( P=0.002) and a 5.1% increase in glycerophosphocholine ( P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. CONCLUSIONS: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.


Methods Find Exp Clin Pharmacol 1997 Apr;19(3):201-10
Citicoline improves memory performance in elderly subjects.


Alvarez XA, Laredo M, Corzo D, Fernandez-Novoa L, Mouzo R, Perea JE, Daniele D, Cacabelos R. EuroEspes Biomedical Research Center, La Coruna, Spain.

Citicoline is a choline donor involved in the biosynthesis of brain phospholipids and acetylcholine extensively used in the treatment of neurodegenerative diseases. In this study we investigated the effects of the oral administration of citicoline alone (C1000:1000 mg/day; C500:500 mg/day) or in combination with nimodipine (C +NI:300 + 90 mg/day) during 4 weeks on memory performance in elderly subjects with memory deficits and without dementia (N = 24; age = 66.12 +/- 10.78 years; MMS score = 31.69 +/- 2.76). Results indicated that citicoline in comparison with placebo improves memory in free recall tasks, but not in recognition tests. A significant improvement in word recall (5.17 +/- 1.1 vs. 3.95 +/- 1.2 omissions; p < 0.005), immediate object recall (6.5 +/- 1.6 vs. 5.5 +/- 1.2 omission; p < 0.05) and delayed object recall (8.5 +/- 2.1 vs. 6.7 +/- 2.4 omissions; p < 0.005) was observed after citicoline treatment. Similar results were found in the three subgroups of treatment (8 subjects per group), suggesting that citicoline possesses memory-enhancing activity at doses of 300-1000 mg/day. A decrease in systolic blood pressure and minor changes in lymphocyte cell counting were also observed in old subjects after receiving citicoline. These effects are consistent with the vasoregulatory and neuroimmune actions of citicoline and suggest that this compound may improve memory by acting on mechanisms of brain neurotropism and cerebrovascular regulation. According to the present results, showing that citicoline improves memory performance in elderly subjects, we concluded that this molecule is suitable for the treatment of memory deficits in old people.


Arch Neurol 1996 May;53(5):441-8
Citicoline improves verbal memory in aging.


Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Clinical Research Center, Massachusetts Institute of Technology, Cambridge, USA.

OBJECTIVE: To test the verbal memory of older volunteers given citicoline. DESIGN: A randomized, double-blind, placebo-controlled, parallel group design was employed in the initial study. After data analysis, a subgroup was identified whose members had relatively inefficient memories. These subjects were recruited for a second study that used a crossover design. The subjects took either placebo or citicoline, 1000 mg/d, for 3 months in the initial study. In the crossover study, subjects took both placebo and citicoline, 2000 mg/d, each for 2 months. SUBJECTS: The subjects were 47 female and 48 male volunteers 50 to 85 years old. They were screened for dementia, memory disorders, and other neurological problems. Of the subjects with relatively inefficient memories, 32 participated in the crossover study. MAIN OUTCOME MEASURE: Verbal memory was tested at each study visit using a logical memory passage. Plasma choline concentrations were measured at baseline; at days 30, 60, and 90 in the initial study; and at day 60 of each treatment condition in the crossover study. Plasma choline concentrations and memory scores were analyzed using repeated-measures analysis of variance and covariance, followed by planned comparisons when appropriate. RESULTS: In the initial study, citicoline therapy improved delayed recall on logical memory only for the subjects with relatively inefficient memories. In the crossover study, the higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory. CONCLUSIONS: Citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories. Citicoline may prove effective in treating age-related cognitive decline that may be the precursor of dementia.


Clin Ter 1991 Jun 30;137(6):403-13
Citicoline in the treatment of cognitive & behavioral disorders in pathologic senile decline


Di Trapani G, Fioravanti M. Clinica Neurologica, Universita Cattolica del Sacro Cuore di Roma.

A three months study was performed on 150 aging patients with primary memory deficits in order to verify the effectiveness of CDP-Choline, administered in repeated cycles of four weeks, with an interval of one week between cycles, in improving patients' cognitive and behavioral efficiency and in stabilizing their cognitive decline. Objective measures of memory and attention, and a behavioral rating scale were used to assess treatment effects. CDP-Choline treatment demonstrated both symptomatic efficacy and a long lasting effect on cognition and behavior of these patients. Level of activation and attention responsiveness improved during treatment cycles and no further changes were identified of these variables in the follow-up period. Measures related to specific memory functioning showed, besides improvements during treatment, after-effects still active in the follow-up period, suggesting a long lasting change of the cognitive decline trend characteristic of these patients.


Ann N Y Acad Sci 1991;640:233-6
Efficacy of CDP-choline in the treatment of senile alterations in memory.


de la Morena E. Fundacion Jimenez Diaz, School of Medicine, Madrid, Spain.

Alterations in membrane function may occur as a consequence of aging because of a decrease in the synthesis or an increase in the catabolism of choline and ethanolamine glycerophospholipids, leading to impairment in cognitive function. Experimental studies have shown that the administration of CDP-choline increases the total amount of phosphatidylcholine and other related phospholipids in the brain and in some cases may enhance neurotransmission. Clinical assessments and neuropsychologic tests in patients with cerebral insufficiency, chronic cerebrovascular disease, and dementia suggest that CDP-choline may improve some of the memory deficits associated with aging.

Minerva Med 1990 Jun;81(6):465-70
Effect of CDP-choline on senile mental deterioration. Multicenter experience on 237 cases


Serra F, Diaspri GP, Gasbarrini A, Giancane S, Rimondi A, Tame MR, Sakellaridis E, Bernardi M, Gasbarrini G. Scuola di Specializzazione in Geriatria e Gerontologia, 1a Cattedra di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Bologna.

The efficacy of CDP-choline (1000 mg/die) administered for two 21-day treatment cycles, with a one-week wash-out period between them, was evaluated in out and in-patients suffering from mild to moderate brain aging. The study was performed on 237 fully evaluable patients with the use of the reduced geriatric scale of Plutchik and al., for clinical evaluation of the symptomatology. The clinical data obtained demonstrate that treatment with CDP-choline is able to determine an improvement of symptomatology since the 1st cycle of therapy (p less than 0.001), and a further improvement in the 2nd cycle (p less than 0.001). Particularly, the therapeutic effect of the 1st cycle is persistent in the intermediate wash-out period (suspension of treatment) with a further decrease, of symptomatology regarding some items of Plutchik's scale (p less than 0.01). Finally, treatment with CDP-choline 1000 mg/die for two 21-day cycles in 237 patients suffering from brain aging determined a statistically significant improvement of the cognitive and behavioural parameters taken into consideration: independence/autonomous life; human relations/social life; interest and attentive capacity; individual behaviour. Therefore citicoline is confirmed as a valid therapeutic remedy for the clinical, functional and social recovery of these patients.


Minerva Med 1983 Apr 7;74(14-15):819-21
Citicoline activity in senile mental decay


Stramba-Badiale M, Scillieri E.

A brief report on the role of neurotransmittors (especially dopamine) depletion in cerebral aging and the development of certain pathological conditions in the elderly is presented. This is followed by a report on the results obtained by the administration of citicoline (500 mg/per diem intramuscularly for 20 days) to a group of 24 elderly patients with senile mental decay. A significant improvement (p less than 0.01) in mental performance was observed in all patients and no side effects were noted.
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LifeMirage
post Apr 07, 2006, 05:49 PM
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CDP-Choline In Alzheimer's Disease


Methods Find Exp Clin Pharmacol 1999 Nov;21(9):633-44
Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion.


Alvarez XA, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez-Novoa L, Corzo L, Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R. EuroEspes Biomedical Research Center, A Coruna, Barcelona, Spain.

Cytidine 5'-diphosphocholine (citicoline) is a an endogenous intermediate in the biosynthesis of structural membrane phospholipids and brain acetylcholine. Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease. In this study we have investigated the efficacy and safety of the treatment with citicoline versus placebo in patients with Alzheimer disease. Thirty patients (age = 73.0 +/- 8.5 years; range = 57-87 years) with mild to moderate senile dementia (GDS: stages 3-6) of the Alzheimer type were included in a double-blind, randomized and placebo-controlled clinical trial. After a 2-week period of drug washout, patients were treated with i) placebo (n = 17; age = 73 +/- 5 years) or ii) 1,000 mg/day of citicoline (n = 13; age = 76 +/- 9 years) for 12 weeks (84 days). Examinations were done at baseline (T0) and after the 12 weeks of treatment (T12). As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Citicoline also increased cerebral blood flow velocities in comparison with placebo (p < 0.05) when transcranial Doppler recordings from both hemispheres were considered together, as well as diastolic velocity in the left middle cerebral artery (p < 0.05). Patients treated with citicoline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left side electrodes), accompanied by a decrease in relative delta activity particularly marked in the left temporal lobe. Significant differences with respect to placebo (p < 0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere. Treatment with citicoline tended to reduce serum IL-1 beta levels, mainly after 4 weeks of administration, with no modified blood histamine content. In addition, neither adverse side effects nor alterations in biological and hematological parameters were induced by citicoline. The present data indicate that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients. According to our results, it seems that citicoline might be a useful treatment in Alzheimer's disease, and that the efficacy of this compound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE.


Ann N Y Acad Sci 1996 Jan 17;777:399-403
Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors.


Cacabelos R, Caamano J, Gomez MJ, Fernandez-Novoa L, Franco-Maside A, Alvarez XA. Institute for CNS Disorders, Basic and Clinical Neurosciences Research Center, La Coruna, Spain.

CDP-choline was given to patients with Alzheimer's disease (AD) at a daily dose of 1000 mg/day p.o. for one month. This compound slightly improved mental performance, tended to reduce theta activity in fronto-temporal regions, increasing alpha power in occipital areas, and enhanced cerebrovascular perfusion by increasing blood flow velocity and reducing pulsatility and resistance indexes. In addition, CDP-choline diminished histamine and interleukin-1 levels in blood and serum, respectively, and increased plasma TNF.


Methods Find Exp Clin Pharmacol 1994 Oct;16(8):597-607
Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease.


Franco-Maside A, Caamano J, Gomez MJ, Cacabelos R. Department of Digital Diagnosis, Basic and Clinical Neurosciences Research Center, La Coruna, Spain.

CDP-choline participates in brain phospholipid metabolism and acts as an endogenous intermediate in a biosynthetic pathway incorporating free choline into phosphatidylcholine and choline plasmalogens in several tissues, including the central nervous system (CNS). In patients with chronic cerebrovascular disorders, CDP-choline reduces the slow delta frequencies and increases alpha activity in spectral electroencephalogram analysis. We have studied the effect of CDP-choline (cytidine-S-diphosphate-choline; 1000 mg/day x 30 days, p.o.) on brain electrical activity mapping and mental performance in 19 Alzheimer's disease (AD) patients (10 males/9 females; age: 66.21 +/- 1.48 years; Mini-Mental State Examination (MMSE): 26.55 +/- 1.22, Spanish version max. score 35). EEG was registered from 19 electrodes placed according to the 10-20 system and digitalized online. Artefact-free 2-s periods were visually selected, submitted to a frequency analysis and averaged across periods. CDP-choline significantly decreased spectral amplitude in the theta band in F4, F8, and T4 electrodes, and did not modify relative power parameters in any of the frequency bands (delta, theta, alpha, beta) as compared to basal recordings. In patients with late-onset AD (LOAD; N = 6; age: 73.5 +/- 1.34 years; MMSE: 28.75 +/- 2.33), CDP-choline tended to increase relative alpha power in O1 and O2 electrodes. No changes were found in early-onset AD patients (EOAD; N = 13; age: 62.85 +/- 1.21 years; MMSE: 25.54 +/- 1.4). We detected a significant improvement in mental performance after 1 month of treatment with CDP-choline in patients with early-onset AD in whom brain electrical activity data correlated with cognitive parameters. It is likely that the bioelectrical changes induced by CDP-choline in AD are the result of its immunogenic and/or neurotrophic activity in the vicinity of the vascular microenvironment.


Methods Find Exp Clin Pharmacol 1994 Apr;16(3):211-8
Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer's disease.


Caamano J, Gomez MJ, Franco A, Cacabelos R. Institute for C.N.S. Disorders, Basic & Clinical Neurosciences Research Center, La Coruna, Spain.

CDP-choline (cytidine-5-diphosphate-choline) is an acetylcholine precursor frequently used in cerebrovascular disorders and psychoorganic syndromes. Furthermore, several authors have demonstrated the positive effects of CDP-choline on cognitive disorders and memory deficits. In the present study, the effects of CDP-choline (1000 mg/day, p.o. for 1 month) on cognition, evaluated by the Mini-Mental State Examination (MMSE) of Folstein et al., and on blood flow velocities, measured by transcranial Doppler ultrasonography (TCD), were investigated in patients with Alzheimer's disease: (AD, n = 20, age: 66.75 +/- 6.73 years, range: 57-78 yr). Cognitive function was measured by means of the MMSE in basal conditions (A) and after 1 month of treatment with CDP-choline ©. TCD measures were taken through the temporal window for right (MCA-R) and left (MCA-L) middle cerebral arteries with a 2 MHz pulsed transducer using a TC-2000S in basal conditions (A), 1 h after the administration of CDP-choline (cool.gif and after 1 month of treatment with CDP-choline ©. MMSE scores were significantly increased (p < 0.005) in patients with early-onset Alzheimer's disease (EOAD) after CDP-choline treatment. Moreover, the orientation subtest significantly increased in the global group of AD patients (p < 0.01) and in EOAD patients (p < 0.02). Significant differences (p < 0.05) were also found in MCA-Land MCA-R measures between recordings. These results suggest that CDP-choline influences cognitive and cerebrovascular function in Alzheimer's disease, probably through a mechanism linked to an immunogenic and/or neurotrophic effect at the microvascular niche.
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LifeMirage
post Apr 07, 2006, 05:50 PM
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CDP-Choline In Glaucoma


Med Sci Monit 2003 Mar;9(3):PI24-8
Oral citicoline treatment improves visual pathway function in glaucoma.


Rejdak R, Toczolowski J, Kurkowski J, Kaminski ML, Rejdak K, Stelmasiak Z, Grieb P. 2nd Department of Ophthalmology, Medical University, Lublin, Poland.

BACKGROUND: Increased latency and reduced amplitude of visual evoked potentials (VEP), frequently encountered in ocular hypertension or open-angle glaucoma, suggest slowed neural conduction in the visual pathways. An improvement in VEP latency and amplitude has been reported following repeated intramuscular injections of citicoline, a neuroprotective drug. Our aim was to find whether citicoline given orally would produce a similar effect. MATERIAL/METHODS: VEP latency and amplitude were measured in 21 glaucomatous eyes prior to and after two bi-weekly courses of citicoline taken orally in a dose of 1 gram/day. The treatment courses were separated by a two-week break; post-treatment VEP measurement was performed two weeks after the end of the second treatment. RESULTS: 62% of the eyes showed a response to the treatment, with VEP latency reduced from 123.5 (3.9 SEM) ms to 111.9 (1.9 SEM) ms (P=0.0008), and VEP amplitude increased from 6.56 (1.39 SEM) to 7.88 (1.16 SEM) (P=0.04). CONCLUSIONS: Citicoline given orally improves visual evoked potentials in some glaucoma patients.


J Neurosci Res 2002 Jan 15;67(2):143-8
Pharmacodynamics of citicoline relevant to the treatment of glaucoma.


Grieb P, Rejdak R. Laboratory of Experimental Pharmacology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.

Citicoline (exogenous CDP-choline) is a nontoxic and well-tolerated drug used in pharmacotherapy of brain insufficiency and some other neurological disorders, such as stroke, brain trauma, and Parkinson's disease. A few reports indicate that citicoline treatment may also be beneficial in glaucoma. Currently glaucoma is considered a neurodegenerative disease in which retinal ganglion cells (RGC) slowly die, likely in the apoptotic mechanism. Endogenous CDP-choline is a natural precursor of cellular synthesis of phospholipids, mainly phosphatydylcholine (PtdCho). Enhancement of PtdCho synthesis may counteract neuronal apoptosis and provide neuroprotection. Citicoline, when administered, undergoes a quick transformation to cytidine and choline, which are believed to enter brain cells separately and provide neuroprotection by enhancing PtdCho synthesis; similar effect may be expected to occur in glaucomatous RGC. Furthermore, citicoline stimulates some brain neurotransmitter systems, including the dopaminergic system, and dopamine is known as a major neurotransmitter in retina and postretinal visual pathways. In a double-blind, placebo-controlled study, treatment of glaucoma resulted in functional improvement in the visual system noted with electrophysiological methods. Development of citicoline as a treatment for glaucoma is indicated.


Ophthalmology 1999 Jun;106(6):1126-34
Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma.


Parisi V, Manni G, Colacino G, Bucci MG. Cattedra di Clinica Oculistica, Universita' di Roma Tor Vergata, Rome, Italy.

PURPOSE: To evaluate the effects of cytidine-5'-diphosphocholine (citicoline) on retinal function and on cortical responses in patients with glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Forty patients with open-angle glaucoma were randomly divided into two age-matched groups: citicoline group ([GC] n = 25) and placebo group ([GP] n = 15). METHODS: The GC patients were treated with Neuroton (citicoline, 1000 mg/day intramuscularly) for 60 days; GP patients were treated with placebo (physiologic solution with additives) for 60 days. After 120 days of washout (day 180), the GC patients were divided into two age-matched groups: in 10 patients (GC1 group) the washout was prolonged for a further 120 days; in 15 patients (GC2 group) a second 60-day period of citicoline treatment was followed by a second 120-day period of washout. At day 180, the washout was extended for another 180 days in GP patients. In all subjects, retinal and cortical responses were evaluated by simultaneous recordings of visual evoked potentials (VEPs) and pattern-electroretinograms (PERGs) at baseline, after 60 days, and after 180 days. At day 300, VEPs and PERGs were also evaluated in GC1 patients, and at 240 and 360 days in GC2 and GP patients. MAIN OUTCOME MEASURES: Visual evoked potential parameters (P100 latency and N75-P100 amplitude); PERG parameters (P50 latency and P50-N95 amplitude); and intraocular pressure. RESULTS: The GP patients displayed similar VEP and PERG parameters in all examinations performed. In GC patients, the treatment with citicoline induced a significant (P < 0.01) improvement of VEP and PERG parameters, and their values were significantly different (P < 0.01) with respect to those of GP patients (P < 0.01). Visual evoked potentials and PERGs, recorded in GC patients after washout, revealed that although there was a worsening trend, the electrophysiologic improvement was still maintained. After a second period of washout, GC1 patients had VEP and PERG parameters similar (P > 0.05) to baseline ones and to those of GP patients. In GC2 patients, a second period of citicoline treatment induced a further (P < 0.01) improvement of VEP and PERG parameters CONCLUSION: Citicoline may induce an improvement of the retinal and of the visual pathway function in patients with glaucoma.


Int Ophthalmol 1989 Jan;13(1-2):109-12
Therapeutic value of citicoline in the treatment of glaucoma (computerized and automated perimetric investigation).


Pecori Giraldi J, Virno M, Covelli G, Grechi G, De Gregorio F. Clinica Oculistica I, Universita Di Roma La Sapienza, Italia.

The favourable neurotrophic effects obtained by means of the intramuscular administration of citicoline, one of the intermediate compounds of phospholipids, on the visual field of patients suffering from open-angle glaucoma are referred. The drug was administered at the dose of 1 gm for ten consecutive days. Visual field was examined by means of central computerized perimetry and automated perimetry. All patients had well controlled intraocular pressure through beta-blockers, but presented characteristic glaucomatous perimetric defects. It is suggested that citicoline might be administered as a useful complement to conventional hypotensive therapy, since it acts positively on the glaucomatous optic nerve damage.

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LifeMirage
post Apr 07, 2006, 05:50 PM
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CDP-Choline Review Studies


Methods Find Exp Clin Pharmacol 1995 Oct;17 Suppl B:1-54
CDP-choline: pharmacological and clinical review.


Secades JJ, Frontera G. F.I.S.A. Medical Department, Barcelona.

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.


Life Sci 1995;56(9):637-60
Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline.


Weiss GB. M. Hurley & Associates, Inc., Murray Hill, New Jersey 07974-1584.

CDP-choline, supplied exogenously as citicoline, has beneficial physiological actions on cellular function that have been extensively studied and characterized in numerous model systems. As the product of the rate-limiting step in the synthesis of phosphatidylcholine from choline, CDP-choline and its hydrolysis products (cytidine and choline) play important roles in generation of phospholipids involved in membrane formation and repair. They also contribute to such critical metabolic functions as formation of nucleic acids, proteins, and acetylcholine. Orally-administered citicoline is hydrolyzed in the intestine, absorbed rapidly as choline and cytidine, resynthesized in liver and other tissues, and subsequently mobilized in CDP-choline synthetic pathways. Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid degradation. Exogenously administered citicoline prevents, reduces, or reverses effects of ischemia and/or hypoxia in most animal and cellular models studied, and acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Thus, considerable accumulated evidence supports use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in conditions such as ischemic and traumatic injuries. Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson's disease, cardiovascular disease, aging, Alzheimer's disease, learning and memory, and cholinergic stimulation.


Arzneimittelforschung 1983;33(7A):1073-80
Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases.


Lozano Fernandez R.

A drug surveillance study has been carried out with oral cytidine diphosphate choline (CDP-choline, citicoline, Somazina) in 2817 patients of all ages, predominating those between 60 and 80 years old. They were suffering from several neurological processes, mainly the vascular cerebral insufficiency and senile involution. Treatment was carried out for between 15 days and 2 months, the mean dose being 6 ml/d. The efficacy of the treatment was determined on the basis of the disappearance, improvement or worsening of clinical manifestations, most frequently shown by patients. The most benefited clinical manifestations by the treatment were: dizziness disappearing in 48.4% of the cases, and improving in 25.2%, cephalea disappearing in 46.5% and improving in 26.7%, insomnia with 38.6% and 24.9%, respectively; depression with 36.9% and 24.1% and memory shortage with 21.2% and 44.7% respectively. The best results were obtained in chronic cerebrovascular insufficiency, the improvements obtained in dizziness, cephalea, insomnia, fatigue and speech troubles being the most important. The safety of the drug was excellent since side effects were observed only in 5.01% of the patients. Among these effects, the most frequently seen were digestive troubles, observed in 3.6% of the cases.
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post Jul 09, 2009, 03:41 AM
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Thank you so much for the well
written and informative article.
You are very generous with your
knowledge. The article was most
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have you heard about Parkinson's treatment



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Is that another from of cell therapy? Check out. I had my aunt undergo stem cell - parkinson's treatment
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