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Citicoline

Citicoline, chemically known as cytidine-5'-diphosphocholine (CDP-choline), is an endogenous nucleotide that serves as a critical intermediate in the biosynthesis of phosphatidylcholine, a major structural phospholipid in cell membranes.^[1]^[2] Upon oral administration, it is rapidly absorbed and crosses the blood-brain barrier, where it hydrolyzes into cytidine (which converts to uridine) and choline, thereby elevating levels of these precursors in the brain to support neurotransmitter synthesis and membrane repair.^[1]^[2] Its pharmacological actions include enhancing acetylcholine production for cholinergic signaling, promoting neuronal membrane integrity and myelin sheath formation, and increasing cerebral metabolism along with levels of neurotransmitters such as norepinephrine and dopamine.^[1]^[2] As a neuroprotective agent, citicoline has been investigated for acute conditions like ischemic stroke and traumatic brain injury, with early studies suggesting potential benefits in accelerating recovery by reducing ischemic lesion volume and mitigating post-traumatic neurological deficits, including coma and cognitive impairments, though recent meta-analyses indicate limited efficacy.^[2]^[3] It is also widely utilized for managing chronic neurodegenerative and cognitive disorders, such as senile cognitive decline secondary to Alzheimer's disease, Parkinson's disease, vascular cognitive impairment, and glaucoma, where it helps preserve memory, vigilance, and visual working memory while potentially slowing dementia progression.^[2]^[1] In addition, citicoline supports cognitive enhancement in healthy aging individuals and has shown benefits in addictive disorders by modulating dopamine and glutamate systems.^[1]^[4] Introduced as a prescription drug in the 1970s primarily in Europe and Japan for neurological applications, citicoline has a well-established safety profile with no significant adverse effects reported at therapeutic doses up to 1,000 mg daily, and it has since gained approval as a dietary supplement in the United States and European Union.^[1] Clinical evidence from randomized controlled trials and meta-analyses, including a 2005 Cochrane review of 7 trials involving over 1,000 patients, supports a small positive role in improving memory and cognitive functions in chronic cerebrovascular disorders; however, in 2025, the European Union rejected authorization for health claims related to cognitive benefits due to insufficient evidence.^[1]^[5]^[6] This underscores its potential as a versatile neurorestorative compound, though evidence varies by application.

Chemical properties

Structure and nomenclature

Citicoline is a nucleotide derivative composed of cytidine linked via a diphosphate bridge to choline, specifically cytidine 5'-diphosphocholine.^[7] Its chemical formula (free base) is C14H26N4O11P2, with a molecular weight of 488.32 g/mol; the sodium salt form used in pharmaceuticals has the formula C14H25N4NaO11P2 and molecular weight of 510.31 g/mol.^[7]^[8] The international nonproprietary name (INN) for the compound is citicoline, while common synonyms include CDP-choline and cytidine 5'-diphosphocholine.^[9]^[7] Citicoline serves as an endogenous intermediate in the Kennedy pathway for the biosynthesis of phosphatidylcholine, a key membrane phospholipid, from choline.^[10]

Physical and chemical characteristics

Citicoline is typically presented as a white to off-white crystalline powder that exhibits hygroscopic properties, readily absorbing moisture from the air.^[11] This form is characteristic of the sodium salt commonly used in pharmaceutical applications, with a melting point ranging from 259°C to 268°C.^[11] In terms of solubility, citicoline demonstrates high water solubility, exceeding 100 mg/mL at room temperature, which facilitates its dissolution to form a clear, acidic solution.^[12] It is practically insoluble in ethanol and most organic solvents, limiting its solubility in non-aqueous media to negligible levels.^[13] Citicoline exhibits good stability under neutral pH conditions (around pH 7), remaining largely intact during storage and formulation processes. However, it is prone to degradation in acidic or alkaline environments, where hydrolysis can occur; oxidative stress also contributes to minor breakdown. To preserve stability, it is recommended to store citicoline in a cool, dry, well-ventilated place, protected from light and moisture, with accelerated stability studies confirming no significant degradation for up to three months at 40°C and 75% relative humidity.^[11]^[14] The ionization behavior of citicoline is governed by its pKa value of 4.4, primarily associated with the diphosphate group, resulting in partial ionization at physiological pH and contributing to its acidic nature in aqueous solutions.^[13]

Medical uses

Stroke and brain injury recovery

Citicoline is employed in the management of acute ischemic stroke, where it is administered intravenously or orally soon after symptom onset to facilitate neurological recovery and improve functional outcomes.^[15] In clinical practice, oral doses starting from 500 mg daily have demonstrated benefits in enhancing general patient condition and post-stroke rehabilitation when initiated early.^[16] Intravenous administration is particularly utilized in acute settings to rapidly achieve therapeutic levels, supporting the restoration of brain function in ischemic events.^[17] A 2025 network meta-analysis of clinical trials found that citicoline doses of 500 mg and 2000 mg improved neurological function and reduced mortality compared to placebo in acute ischemic stroke patients.^[18] For traumatic brain injury (TBI), citicoline shows potential in mild to moderate cases by helping to mitigate cerebral edema and promote better overall recovery. Studies indicate that its use in TBI can lead to reductions in brain swelling as observed through neuroimaging, alongside improvements in clinical symptoms during the acute and subacute phases.^[19] This application focuses on stabilizing the injury site and aiding in the resolution of secondary damage following head trauma. Regulatory approval for citicoline in stroke and related cerebrovascular disorders exists in Japan, where it was originally developed, and in several European countries for acute ischemic stroke treatment.^[20] In contrast, it lacks approval from the U.S. Food and Drug Administration (FDA) as a prescription drug for these indications. In the United States, it is available and legally marketed as a dietary supplement as of 2025.^[21]^[22] Typical dosing for stroke and brain injury recovery involves 500 to 2000 mg per day, often divided into multiple administrations during the acute and recovery periods.^[23] Pooled analyses from clinical trials support its efficacy in these regimens for aiding recovery.^[15]

Glaucoma and vision disorders

Citicoline has been investigated as an adjunct therapy in glaucoma management, particularly for preserving retinal ganglion cells (RGCs) and mitigating visual field loss in primary open-angle glaucoma (POAG).^[24] As a neuroprotective agent, it is administered orally or topically to support optic nerve function and slow disease progression beyond intraocular pressure (IOP) reduction alone.^[25] Clinical studies suggest it may enhance retinal bioelectrical responses and stabilize structural parameters like retinal nerve fiber layer (RNFL) thickness, though evidence remains preliminary and mixed.^[26] In oral formulations, citicoline is typically dosed at 500–1000 mg per day, either continuously or in cycles, with effects on visual function often emerging after at least one year of use.^[24] A pilot randomized study of 60 POAG patients over two years found that oral citicoline therapy stabilized mean deviation (MD) on standard automated perimetry at -7.25 dB at 18 months, compared to worsening in controls (-9.28 dB at 24 months), alongside preserved RNFL (70.39 μm at 12 months) and ganglion cell complex (GCC) thicknesses.^[26] Another trial involving 41 patients with progressing glaucoma (baseline MD progression of -1.1 dB/year) reported a reduced rate to -0.15 dB/year after two years of oral citicoline supplementation, despite stable IOP around 15.5 mmHg.^[27] These findings indicate potential benefits in slowing visual field deterioration and supporting RGC survival through optic nerve protection.^[28] Topical citicoline eye drops have also shown promise in enhancing retinal function and neural conduction in OAG. In a study of 24 treated eyes (3 drops/day for 4 months), pattern electroretinogram (PERG) P50-N95 amplitude increased significantly (p < 0.01), as did visual evoked potential (VEP) N75-P100 amplitude, with shortened VEP P100 implicit time, correlating with improved PERG responses; effects reversed after a 2-month washout.^[29] Such improvements suggest citicoline aids in preserving visual acuity and pathway conduction in early to moderate glaucoma.^[25] Despite these observations, a 2023 systematic review of 10 clinical studies (424 patients, mean follow-up 12.1 months) concluded there is insufficient evidence to confirm citicoline slows glaucoma progression, with no significant differences in IOP, MD, RNFL, or PERG amplitudes versus controls.^[30] Nonetheless, it is recommended as an adjunct in progressive cases to improve quality of life, cognitive adherence to therapy, and overall neuroprotection, without reported side effects at standard doses.^[24]

Cognitive enhancement and neurodegenerative conditions

Citicoline is used as an over-the-counter supplement to support cognitive function in cases of age-related memory decline, with clinical evidence indicating improvements in memory performance among healthy older adults experiencing age-associated memory impairment. A randomized, double-blind, placebo-controlled trial demonstrated that 12 weeks of daily supplementation with 500 mg citicoline enhanced overall memory, particularly episodic memory, in individuals aged 50 to 85 years with self-reported memory complaints. The European Food Safety Authority evaluated evidence for a health claim on citicoline's role in maintaining or reducing memory loss but concluded that a cause-and-effect relationship has not been established.^[31]^[32]^[33] In patients with mild cognitive impairment, especially of vascular origin, citicoline has shown consistent improvements in cognitive function, including memory and behavioral aspects, over medium-term treatment periods of several months.^[31]^[33] In Alzheimer's disease, citicoline has been investigated for its potential to provide moderate cognitive benefits, particularly in memory domains, through cholinergic support that may slow disease progression. Multiple trials, including those in patients with Alzheimer's and mixed dementia, have reported positive effects on cognitive performance when citicoline is used as an adjunct therapy, with one study confirming effectiveness in improving mental status over 12 months at doses of 1,000 mg daily. However, while pilot studies suggest benefits, larger-scale confirmatory trials are lacking to establish definitive efficacy. For Parkinson's disease, citicoline serves as an adjuvant therapy that enhances dopaminergic function, allowing reductions in levodopa dosage by up to 50% while improving cognitive status, rigidity, and motor symptoms. A systematic review of clinical studies highlighted significant enhancements in overall neurological function, including handwriting and speech, with negligible side effects over treatment durations of 30 days to several months.^[34]^[35]^[36]^[37]^[38] Citicoline is also under investigation for other cognitive and neurodegenerative conditions, including attention-deficit/hyperactivity disorder (ADHD), depression, and multi-infarct dementia, where it may support neurotransmitter modulation and neuronal repair. In multi-infarct dementia, administration of 1,000 mg daily for three months has improved mental performance as assessed by standardized scales. Preliminary evidence points to potential benefits in ADHD and depression through enhanced cholinergic and dopaminergic pathways, though robust clinical trials remain limited. As a supplement, citicoline is commonly available in capsule form at doses of 250 to 500 mg, often taken once or twice daily for brain health support, with typical regimens ranging from 500 to 2,000 mg per day divided into doses.^[39]^[40]^[39]^[41]^[42]

Research evidence

Clinical trials on stroke

Clinical trials investigating citicoline for stroke recovery have primarily focused on its potential neuroprotective effects in acute ischemic stroke, evaluating outcomes such as functional independence, neurological deficits, and mortality. Early smaller trials suggested benefits in reducing infarct size and improving recovery, but larger studies have yielded mixed results.^[43] The landmark International Citicoline Trial on Acute Stroke (ICTUS), a multicenter, randomized, placebo-controlled trial conducted from 2006 to 2011, enrolled 2,298 patients with moderate-to-severe acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) and administered intravenous citicoline (1,000 mg every 12 hours) or placebo for up to 5 days, followed by oral administration for 3 weeks. The primary outcome, global diagnostic scale assessment at 90 days, showed no significant difference between groups (common odds ratio 1.04, 95% CI 0.89-1.21), indicating no overall benefit in functional recovery. Secondary outcomes, including modified Rankin Scale and Barthel Index, also failed to demonstrate superiority of citicoline, though the treatment was well-tolerated with no increase in adverse events.^[15] The Citicoline Brain Injury Treatment (COBRIT) trial, a phase 3 randomized study from 2007 to 2011 involving 1,213 patients with traumatic brain injury (including a subset with comorbid ischemic events), tested oral and intravenous citicoline (2,000 mg/day) for 90 days versus placebo. While primarily targeting traumatic brain injury, the trial's findings are relevant for stroke-like brain injury recovery; it reported no improvement in functional status (Extended Glasgow Outcome Scale) or cognitive performance at 90 or 180 days, with similar safety profiles across groups.^[44]^[45] A 2012 Cochrane review of 9 randomized trials (n=4,056) found no evidence of benefit from citicoline in reducing all-cause mortality (risk ratio 0.98, 95% CI 0.82-1.17) or improving functional outcomes (odds ratio 1.08 for poor outcome on modified Rankin Scale, 95% CI 0.94-1.23), with low-certainty evidence overall. An updated 2023 meta-analysis of citicoline specifically across 12 randomized trials (n=4,914) found significant improvements in neurological recovery and functional outcomes in acute stroke (e.g., odds ratio 0.72 for good functional outcome on modified Rankin Scale, 95% CI 0.60-0.86), but no mortality benefit, attributing variability to differences in administration timing and patient severity.^[46]^[47] Post-2020 studies have explored long-term administration, with a 2022 randomized trial (n=100) showing that 8 weeks of oral citicoline (1,000 mg/day) after acute ischemic stroke improved intracortical excitability and partial functional measures via transcranial magnetic stimulation, suggesting potential adjunctive benefits in rehabilitation phases. A 2023 observational study indicated that prolonged citicoline use (1 g/day for 12 months) prevented post-stroke cognitive decline in vascular patients, enhancing quality of life without safety concerns.^[48]^[49] Limitations across trials include heterogeneity in dosing regimens (500-2,000 mg/day, acute vs. chronic), timing of initiation (within 24 hours to 14 days post-stroke), and patient populations (varying stroke severity and comorbidities), which complicate direct comparisons and contribute to inconsistent outcomes. Evidence as of early 2025 shows no major shifts from these findings.^[47]

Studies on vision and glaucoma

Research on citicoline in glaucoma has primarily focused on its potential neuroprotective effects on retinal ganglion cells and visual function, with several randomized controlled trials (RCTs) examining outcomes such as visual field preservation and contrast sensitivity. A 2020 RCT involving 90 patients with progressing open-angle glaucoma found that adjunctive treatment with 2% citicoline eye drops, alongside intraocular pressure-lowering therapy, significantly reduced the rate of visual field deterioration compared to placebo, with mean deviation progression slowing from -1.48 dB/year to -0.4 dB/year over three years. Similarly, a 2022 multicenter RCT in early glaucoma patients demonstrated that oral citicoline (500 mg/day) combined with other supplements improved pattern electroretinogram (PERG) parameters, indicative of enhanced retinal function and contrast sensitivity, after six months of treatment. These findings suggest citicoline may stabilize visual function in progressive cases, though results vary by administration route and patient stage. A 2023 systematic review of 10 clinical studies (n=424) encompassing RCTs and observational trials from 1989 to 2022 analyzed citicoline's impact on glaucoma progression, including visual field metrics via mean deviation (MD 24-2) and retinal nerve fiber layer thickness. The review reported no overall significant improvement in visual field progression (P=0.7) or contrast sensitivity-related PERG amplitudes (P=0.2), attributing heterogeneity to differences in dosing, duration, and study design; however, it highlighted positive trends in smaller RCTs for adjunctive use in stabilizing early visual loss. Earlier seminal work, such as a 2013 RCT (n=46), showed oral citicoline (500 mg/day in cycles) reduced visual field loss rates to -0.15 dB/year over two years in primary open-angle glaucoma, supporting its role in slowing progression when intraocular pressure is controlled. The 2024 FASEB Journal review on citicoline's neuroprotective mechanisms emphasized its role in retinal protection, citing a pilot study where 2% citicoline eye drops slowed visual field changes and preserved retinal structure in glaucoma patients over 180 days by enhancing phospholipid synthesis and reducing oxidative stress in retinal ganglion cells. In progressive glaucoma, data from a 2017 review of multiple trials indicated citicoline acts as a neuroprotector, particularly benefiting patients with ongoing visual field defects despite optimal pressure management, by improving neural conduction along the visual pathway. For pediatric applications, a 2018 pilot study (n=20) in children with visual impairment (including some with optic nerve involvement akin to early glaucoma) reported modest, non-significant gains in high- and low-contrast visual acuity after oral citicoline (250-500 mg/day for three months), suggesting potential for early intervention but requiring larger trials to confirm benefits in juvenile glaucoma. Despite these insights, research gaps persist, including the need for larger, long-term RCTs to evaluate citicoline's efficacy in preserving vision beyond two years and across diverse glaucoma subtypes, as current evidence is limited by small sample sizes and inconsistent endpoints. Ongoing multicenter trials, such as a 2022-registered study (n=60) assessing citicoline eye drops' impact on visual field in open-angle glaucoma, aim to address these limitations by providing blinded, prospective data on morpho-functional outcomes.

Evidence for cognitive and other neurological applications

Citicoline has demonstrated positive effects on memory function in elderly individuals, particularly in randomized controlled trials involving healthy older adults. For instance, supplementation with 500–1000 mg/day for 12 weeks improved episodic and verbal memory performance, as measured by tools like the Paired Associates Learning test, in participants with age-associated memory impairment.^[1] A 2022 review of pharmacological evidence further supports these findings, noting consistent improvements in cognitive efficacy among cognitively normal middle-aged and elderly persons, attributed to enhanced brain choline uptake.^[50] In Alzheimer's disease, evidence from randomized controlled trials remains limited and of low quality, with small sample sizes and short durations hindering definitive conclusions. A 2023 systematic review and meta-analysis of seven studies found citicoline improved Mini-Mental State Examination (MMSE) scores by approximately 1.5 points in patients with mild Alzheimer's, but high risks of bias and inconsistent methodologies tempered the results.^[51] Similarly, trials in mild cognitive impairment, often vascular in origin, reported moderate cognitive enhancements, though benefits were more pronounced when combined with standard therapies.^[52] For neurodegenerative conditions like Parkinson's disease, citicoline enhances dopamine synthesis and inhibits its reuptake, leading to symptom improvements in adjuvant therapy. A 2020 systematic review of seven studies showed significant reductions in rigidity, akinesia, and tremor, alongside up to 50% lower levodopa requirements and better cognitive status.^[37] Emerging real-world applications in 2025 include its use for attention-deficit/hyperactivity disorder (ADHD), where a 2024 pilot study indicated benefits in attention and impulsivity as an adjunct treatment, though larger trials are needed to confirm efficacy.^[53] Preliminary data suggest potential roles in other neurological applications, such as depression and multiple sclerosis. In major depressive disorder, a double-blind trial found citicoline as an adjuvant reduced Hamilton Depression Rating Scale scores, enhancing response to antidepressants.^[54] For multiple sclerosis, preclinical and early clinical evidence points to citicoline's promotion of remyelination and reduction of inflammation, with a 2021 review proposing it as an adjunct to improve visual evoked potentials and cognitive decline.^[55] A 2020 systematic review in PubMed Central analyzed citicoline's role across neurological disorders, highlighting inconsistent yet promising results for cognitive applications, including dementia prevention and enhancement in healthy aging, based on 20+ studies emphasizing its neuroprotective profile.^[56] Overall, while results are encouraging, the evidence base calls for more robust, large-scale trials to establish optimal dosing and long-term outcomes. Evidence as of early 2025 shows no major shifts from these findings.

Mechanism of action

Neuroprotective mechanisms

Citicoline exerts neuroprotective effects primarily through its antioxidant properties, which mitigate oxidative stress in ischemic and degenerative conditions. It reduces the production of reactive oxygen species (ROS) and enhances the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), thereby protecting neuronal cells from free radical damage.^[57] In models of cerebral ischemia, citicoline increases glutathione levels and attenuates lipid peroxidation, preserving cellular integrity against oxidative injury.^[58] Additionally, citicoline demonstrates anti-apoptotic actions by inhibiting key pathways of programmed cell death in neurons. It decreases the expression and activation of pro-apoptotic proteins like Bax and caspases-3 and -9, while upregulating anti-apoptotic factors such as Bcl-2, particularly in response to ischemic insults or ocular hypertension.^[57] These effects help prevent neuronal loss during reperfusion following brain injury, contributing to overall tissue preservation.^[58] Citicoline supports neuronal energy metabolism, which is crucial for survival under hypoxic or ischemic conditions. By promoting phosphatidylcholine synthesis, it enhances mitochondrial function, cerebral blood flow, and glucose utilization, thereby facilitating ATP production and maintaining cellular homeostasis.^[57] This metabolic stabilization restores activities of energy-dependent enzymes like Na+/K+-ATPase, countering the bioenergetic failure associated with neurodegeneration.^[58] At the molecular level, citicoline influences key neuroprotective pathways through the upregulation of genes and proteins that promote cell survival and repair. It increases expression of SIRT1, a sirtuin involved in reducing inflammation and oxidative damage, with effects observed in stroke models where SIRT1 inhibition abolishes citicoline's benefits.^[59] Furthermore, citicoline upregulates brain-derived neurotrophic factor (BDNF), supporting neurogenesis and synaptic plasticity in affected neural tissues.^[57]

Neuronal membrane stabilization

Citicoline, also known as CDP-choline, serves as a critical precursor in the biosynthesis of phosphatidylcholine, a major phospholipid component of neuronal cell membranes. By providing cytidine and choline moieties, it facilitates the synthesis of phosphatidylcholine through the Kennedy pathway, thereby increasing membrane phospholipid levels and enhancing overall membrane integrity.^[60]^[61] This process not only supports the structural maintenance of neuronal membranes but also inhibits phospholipid breakdown, preserving membrane fluidity and function during physiological stress.^[61] In scenarios of neuronal injury, such as ischemia or trauma, citicoline promotes the repair and restoration of membrane integrity by replenishing depleted phospholipids and mitigating lipid degradation. Post-ischemic administration in animal models has been shown to restore phosphatidylcholine and sphingomyelin levels, key constituents of the outer membrane leaflet, while reducing arachidonic acid release that exacerbates oxidative damage.^[62]^[63] This reparative action is essential for recovery from stroke or head trauma, where membrane disruption leads to cellular swelling and functional deficits.^[64]^[61] Citicoline also contributes to the support of the myelin sheath by enhancing oligodendrocyte function and promoting remyelination. In demyelinating models like experimental autoimmune encephalomyelitis and cuprizone-induced injury, citicoline increases the proliferation of oligodendrocyte precursor cells and mature oligodendrocytes, leading to improved myelin regeneration and reversal of motor impairments.^[65]^[55] These effects underscore its role in maintaining the insulating properties of neuronal axons. The biochemical pathway underlying these actions begins with the hydrolysis of citicoline into cytidine and free choline, which is then rapidly absorbed and utilized in tissues. The liberated choline serves as a substrate for phosphocholine formation, which combines with cytidine triphosphate to regenerate CDP-choline; this intermediate reacts with diacylglycerol—derived from phosphatidic acid—to yield phosphatidylcholine, directly bolstering membrane repair.^[61]^[63] This pathway ensures efficient delivery of components for membrane phospholipid turnover, particularly in the brain where citicoline crosses the blood-brain barrier to support localized synthesis.^[61]

Neurotransmitter and signaling modulation

Citicoline, also known as CDP-choline, modulates several key neurotransmitter systems in the brain, influencing synthesis, release, and uptake to support neuronal signaling. By providing cytidine and choline as precursors, it enhances the production and availability of neurotransmitters such as dopamine, acetylcholine, norepinephrine, and serotonin, while also regulating glutamate levels to prevent excitotoxic damage.^[56] These actions contribute to improved synaptic function and neuroprotection in various neurological contexts. Regarding dopamine, citicoline increases its synthesis by elevating tyrosine levels in the striatum and stimulating tyrosine hydroxylase activity, the rate-limiting enzyme in catecholamine biosynthesis. It also promotes dopamine release from nigrostriatal neurons and may inhibit its reuptake, thereby enhancing dopaminergic transmission in regions like the corpus striatum. These effects have been observed in both animal models and human studies, particularly in conditions involving dopaminergic deficits.^[4]^[66] In cholinergic signaling, citicoline serves as a direct precursor for acetylcholine synthesis by donating choline, which is transported into neurons via the high-affinity choline transporter and utilized by choline acetyltransferase. This boosts acetylcholine levels, supporting memory, attention, and cognitive processes, without causing acute cholinergic toxicity due to regulated metabolism. Clinical and preclinical evidence demonstrates that citicoline administration elevates brain acetylcholine content, enhancing cholinergic pathway activity.^[67]^[68]^[66] Citicoline further impacts glutamate transport by enhancing astrocytic uptake through upregulation of the excitatory amino acid transporter 2 (EAAT2), which increases clearance of extracellular glutamate and mitigates excitotoxicity. In cultured astrocytes and ischemic models, citicoline at concentrations around 100 μM elevates glutamate uptake rates and transporter expression, reducing neuronal vulnerability to glutamate-induced apoptosis and synaptic damage.^[69]^[70]^[71] For other monoamine pathways, citicoline elevates norepinephrine levels in the cerebral cortex and hypothalamus, supporting arousal and stress responses, while increasing serotonin in various brain regions to promote mood regulation and neuroprotection. These modulations occur through enhanced synthesis and reduced turnover of these neurotransmitters, as evidenced in rodent studies and reviews of its pharmacological profile.^[4]^[56]^[72]

Pharmacokinetics

Absorption, distribution, and metabolism

Citicoline demonstrates high oral bioavailability of approximately 90-92% after oral administration, indicating efficient uptake from the gastrointestinal tract. It is rapidly absorbed, with nearly complete absorption occurring and less than 1% of the dose recovered in feces over several days.^[73]^[74] Following absorption, citicoline is widely distributed throughout the body, readily crossing the blood-brain barrier to enter the central nervous system. The highest concentrations are observed in the brain, where up to 62.8% of the total radioactivity is incorporated into phospholipids, and in the liver, which plays a key role in initial processing.^[73]^[75] Metabolically, citicoline undergoes hydrolysis primarily in the intestinal wall and liver, breaking down into cytidine and choline. The cytidine moiety is further converted to uridine, allowing these components to participate in subsequent biochemical pathways. Plasma concentrations of citicoline and its metabolites exhibit a biphasic profile, with an initial peak occurring 1-2 hours post-dose.^[76]^[74]

Elimination and half-life

Citicoline is rapidly hydrolyzed to its primary metabolites, choline and cytidine, which are subsequently eliminated mainly through urinary excretion and respiration as carbon dioxide (CO₂), with less than 1% recovered in feces.^[77]^[78] The elimination half-life of the parent citicoline compound is short, approximately 3.5 hours for the initial phase, reflecting its quick conversion to metabolites.^[79] In contrast, the metabolites exhibit longer half-lives of 50-70 hours, specifically 56 hours for respiratory CO₂ and 71 hours for urinary excretion.^[77]^[80] Clearance of citicoline and its metabolites occurs primarily via renal mechanisms due to urinary excretion, with renal function playing a key role in the process; hepatic metabolism contributes to biotransformation but does not significantly affect overall elimination.^[77]^[78]

Safety and side effects

Adverse effects and tolerability

Citicoline is generally well-tolerated, with clinical trials demonstrating a favorable safety profile and fewer adverse effects compared to placebo, particularly in elderly populations.^[4] Common adverse effects are mild and primarily involve gastrointestinal disturbances, such as nausea, stomach pain, and diarrhea, occurring in approximately 4% of patients across large cohorts. Transient headaches have also been reported at similar low incidences. These effects are typically self-limiting and do not necessitate discontinuation of treatment.^[4] Rarer side effects include restlessness or insomnia, hypotension, tachycardia, and bradycardia, with cardiovascular symptoms noted in less than 1% of cases in comprehensive reviews of over 2,800 patients. No serious toxicity has been observed at doses up to 2,000 mg/day, and citicoline exhibits negligible overall toxicity, with high LD50 values in preclinical models (e.g., >4,000 mg/kg intravenously in rodents).^[4]^[76]^[39] In long-term clinical trials, citicoline has been well-tolerated without evidence of genotoxicity or carcinogenicity, showing no carcinogenic potential in animal studies and minimal adverse events even in extended use for neurological conditions.^[76] Drug interactions with citicoline are minimal and not well-documented, though caution is advised with cholinergic agents due to its role as a precursor that may potentiate effects like those of L-dopa.^[39]^[76]

Dosage recommendations and contraindications

Citicoline is typically administered orally at doses of 500 to 1000 mg per day for cognitive enhancement and mild cognitive impairment, often divided into two doses to maintain steady plasma levels.^[52] For acute ischemic stroke, higher doses up to 2000 mg per day are used, which may be given intravenously initially (e.g., 1000 to 2000 mg daily for the first few days) followed by oral maintenance.^[81] Treatment duration generally ranges from 4 to 12 weeks for most neurological indications, though some studies extend to 6 months or longer for post-stroke recovery without evidence of increased risk.^[39]^[81] Contraindications to citicoline use include known hypersensitivity to the drug or its components, as allergic reactions may occur.^[39] It should be avoided in cases of intracerebral hemorrhage or brain tumors, based on exclusion criteria in clinical trials for stroke.^[81] Precautions are advised during pregnancy and lactation due to limited data on safety and efficacy, with no adequate controlled studies available; use only if potential benefits outweigh risks.^[39] In patients with renal impairment, dosage adjustment may be necessary in mild-to-moderate cases or among the elderly with reduced function, though some evidence suggests no specific modification is required.^[82] No routine laboratory monitoring is needed for standard use, given its favorable tolerability profile.^[39]

Synthesis

Chemical synthesis methods

Citicoline, chemically known as cytidine 5'-diphosphocholine, was first synthesized in 1956 by Eugene P. Kennedy and colleagues through a chemical route involving the activation of cytidine nucleotides and coupling with choline derivatives.^[83] This seminal work laid the foundation for laboratory and industrial production methods, focusing on forming the diphosphate bridge between cytidine and choline moieties.^[84] The primary chemical synthesis route entails the condensation of cytidine 5'-monophosphate (CMP) with phosphorylcholine, facilitated by either chemical or enzymatic activation of the phosphate group. In chemical activation, CMP is typically converted to an activated intermediate, such as a morpholidate or imidazolide, before coupling. For instance, one established method reacts CMP with morpholine in the presence of a coupling reagent like dicyclohexylcarbodiimide (DCC) to form cytidine 5'-phosphomorpholidate, which is then condensed with calcium phosphorylcholine chloride under anhydrous conditions to yield citicoline.^[85] An alternative chemical activation employs carbonyldiimidazole (CDI) to form a reactive imidazolide from CMP in dimethylformamide, followed by addition of zinc chloride and phosphorylcholine for the coupling step at room temperature.^[86] Key steps in these chemical syntheses include phosphate activation to enable nucleophilic attack by phosphorylcholine, followed by phosphorylation to establish the diphosphate linkage, and purification without extensive protection of the ribose hydroxyl groups, as the selectivity of activation minimizes side reactions. Deprotection is generally unnecessary in the standard CMP route, though any transient protecting groups on phosphate or hydroxyls are removed via hydrolysis or ion exchange during workup. Yields typically range from 70-80% after chromatographic purification and conversion to the sodium salt via anion-exchange resin.^[87] Enzymatic activation, using isolated enzymes like choline kinase or cytidylyltransferase in vitro, offers a milder alternative for lab-scale production, mirroring chemical steps but with higher specificity and reduced byproducts.^[88] For industrial production of pharmaceutical-grade citicoline, chemical synthesis methods are optimized for scalability, incorporating precise control of reaction temperatures (e.g., 0-50°C), anhydrous solvents like acetonitrile or DMF, and purification techniques such as ion-exchange chromatography and crystallization with dicarboxylic acids to achieve >99% purity.^[89] Yield optimization focuses on minimizing impurities like unreacted CMP or diphosphate hydrolysis products through stoichiometric reagent control and automated process monitoring, enabling cost-effective large-scale output for drug formulations.^[85]

In vivo biosynthesis

Citicoline, also known as cytidine diphosphate-choline (CDP-choline), is endogenously produced in mammalian cells as a key intermediate in the Kennedy pathway, which is the primary route for the de novo synthesis of phosphatidylcholine, a major component of cell membranes. The biosynthetic process initiates with the phosphorylation of free choline to phosphocholine, catalyzed by choline kinase (CHKA or CHKB isoforms), utilizing ATP as the phosphate donor. This is followed by the rate-limiting step, where phosphocholine reacts with cytidine triphosphate (CTP) to form citicoline and pyrophosphate, mediated by CTP:phosphocholine cytidylyltransferase (CCT, encoded by PCYT1A or PCYT1B).^[90]^[91] Subsequently, citicoline serves as the activated donor in the final step of the pathway, transferring its phosphocholine moiety to diacylglycerol via cholinephosphotransferase (CPT1 or CEPT1) to yield phosphatidylcholine. This sequence ensures efficient phospholipid assembly, supporting membrane biogenesis and repair, particularly in response to cellular demands for lipid remodeling. The Kennedy pathway predominates over alternative routes like the CDP-diacylglycerol pathway in most tissues, accounting for the majority of phosphatidylcholine production under normal conditions.^[90]^[91] Regulation of citicoline biosynthesis occurs mainly at the CCT step through feedback mechanisms tied to cellular phosphatidylcholine levels. Elevated phosphatidylcholine concentrations induce positive membrane curvature stress, which inhibits CCT translocation from the cytosol to the endoplasmic reticulum membrane, where it becomes active; conversely, depletion of phosphatidylcholine or accumulation of diacylglycerol promotes CCT activation and citicoline formation. This allosteric and compartmental control maintains phospholipid homeostasis and prevents overproduction.^[91]^[92] Endogenous citicoline synthesis is distributed across various tissues but is particularly prominent in the liver and brain, where high expression of pathway enzymes supports intensive membrane turnover and neuronal function. In the liver, it facilitates systemic lipid metabolism, while in the brain, isoforms like CCTβ and CHKB enable localized phosphatidylcholine synthesis essential for synaptic integrity and myelin maintenance. Daily production aligns with overall choline flux to meet baseline membrane requirements, though exact rates vary with dietary intake and physiological state.^[91]^[90]

References

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Citicoline for Supporting Memory in Aging Humans - PubMed Central
CDP-choline from an exogenous source, known as citicoline, has been used in medicine since the 1970-s as a prescription drug displaying neuroprotective effects, ...
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Citicoline: pharmacological and clinical review, 2006 update - PubMed
The other major indication of citicoline is for treatment of senile cognitive impairment, either secondary to degenerative diseases (e.g. Alzheimer disease) or ...
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Citicoline in Addictive Disorders: A Review of the Literature - PMC
Jun 20, 2014 · Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders such as stroke and dementia.
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Citicoline | C14H26N4O11P2 | CID 13804 - PubChem - NIH
Molecular Formula. C14H26N4O11P ; Synonyms. citicoline; cytidine 5'-diphosphocholine; 987-78-0; CDP-choline; citicholine ; Molecular Weight. 488.32 g/mol.Missing: nomenclature | Show results with:nomenclature
[5]
Citicoline (International database) - Drugs.com
Generic Names · Citicolina (OS: DCIT) · Citicoline (OS: JAN) · Citidoline (OS: DCF) · CDPC (IS) · CDP-Cholin (IS) · Cytidine diphosphate choline (IS) · Cytifin(5') ...Missing: nomenclature | Show results with:nomenclature
[6]
Citicoline: Uses, Interactions, Mechanism of Action | DrugBank Online
Oct 20, 2016 · Citicoline is an endogenous intermediate in the formation of phosphatidylcholine from choline which is thought to have neuroprotective effects.Missing: nomenclature | Show results with:nomenclature
[7]
[PDF] Design development and evaluation of citicoline controlled release ...
Its melting point was 259 - 268°C and dissociation constant (Pka) was 4.4 [1]. Biopharmaceutical classification system (BCS) for Citicoline is Class – I (High ...
[8]
Citicoline sodium | 33818-15-4 - ChemicalBook
Citicoline sodium Properties ; H2O: 100mg/mL · solid · white · yeast · Soluble in water (100 mg/ml).
[9]
Citicoline
Dissolves readily in water to form acidic soln. Practically insol in most organic solvents. pKa 4.4. LD50 in mice, rats (mg/kg): 4600 ±335, 4150 ±370 i.v. ...
[10]
https://go.drugbank.com/drugs/DB12153
[11]
Citicoline in the treatment of acute ischaemic stroke - PubMed
Jul 28, 2012 · Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis.
[12]
Retrospective and observational study to assess the efficacy of ...
It has been shown that, even soon after an ischemic stroke, administration of oral citicoline (500-4000 mg/day) improves the general conditions evaluated with ...<|separator|>
[13]
ICTUS Study: International Citicoline Trial on Acute Stroke
Citicoline is a safe drug approved in some countries for the treatment of acute ischemic stroke. The drug has shown some evidence of efficacy in a pooled ...
[14]
Citicoline for the Management of Patients with Traumatic Brain Injury ...
Jan 29, 2023 · Citicoline or CDP-choline is a neuroprotective/neurorestorative drug used in several countries for the treatment of traumatic brain injury (TBI).Missing: chemical | Show results with:chemical<|control11|><|separator|>
[15]
Cytidine 5′-Diphosphocholine (CDP-Choline) in Stroke and Other ...
There have been 13 stroke clinical trials of CDP-choline since 1980 (nine in Europe and Japan and four in the USA) (5). The European clinical trials showed that ...
[16]
Citicoline for treating people with acute ischemic stroke
Aug 29, 2020 · Since 17 April 2009, citicoline has been banned in the USA and Canada (Chen 2016; FDA 2019). ... approval of citicoline, we also searched the ...
[17]
Oral Citicoline in Acute Ischemic Stroke
Citicoline treatment at 500 and 2000 mg/d demonstrated significant improvement of neurological (National Institutes of Health Stroke Scale [NIHSS]), functional ...
[18]
[The role of citicoline in glaucoma] - PubMed
Mar 17, 2021 · Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients.Missing: evidence | Show results with:evidence
[19]
Citicoline: A Food Beneficial for Patients Suffering from or Threated ...
Apr 8, 2016 · Experimental data, and also few clinical studies indicate that this substance has potential to counteract some important pathological mechanisms ...Missing: evidence | Show results with:evidence
[20]
Morphological and Functional Evaluation of Oral Citicoline Therapy ...
Sep 26, 2019 · Conclusion: These findings suggest that CT therapy seems to be effective in slowing POAG progression. Further studies on a larger population and ...Missing: clinical evidence
[21]
Citicoline oral solution in glaucoma: is there a role in slowing ...
Conclusions: This study seems to indicate that supplementation with citicoline might significantly slow down glaucomatous rates of progression.Missing: evidence | Show results with:evidence
[22]
The neuroprotective role of citicoline treatment in glaucoma - PubMed
Conclusions. The study of the parameters and their correlations demonstrated that citicoline had positive effects in glaucoma on certain aspects, data ...Missing: evidence | Show results with:evidence
[23]
Treatment with citicoline eye drops enhances retinal function and ...
Conclusions: Topical treatment with citicoline in OAG eyes induces an enhancement of the retinal bioelectrical responses (increase of PERG amplitude) with a ...Missing: clinical | Show results with:clinical<|control11|><|separator|>
[24]
Efficacy of citicoline as a supplement in glaucoma patients - PubMed
Sep 28, 2023 · Conclusion: There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.
[25]
Citicoline and Memory Function in Healthy Older Adults
May 12, 2021 · The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging.
[26]
'Citicoline' and support of the memory function: Evaluation of a ...
Jul 4, 2024 · Improvement, maintenance or reduced loss of memory is a beneficial physiological effect for middle-aged or elderly adults encountering age- ...Abstract · DATA AND METHODOLOGIES · ASSESSMENT · CONCLUSIONS
[27]
Role of Citicoline in Patients With Mild Cognitive Impairment
Feb 16, 2023 · Citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin.
[28]
Citicoline in Vascular Cognitive Impairment and Vascular Dementia ...
Dec 16, 2010 · Citicoline has been used in a number of trials in patients with Alzheimer disease and has shown consistent but moderate improvement of memory ...Missing: age- | Show results with:age-
[29]
Citicoline: A Cholinergic Precursor with a Pivotal Role in Dementia ...
Jun 15, 2024 · This study confirmed the effectiveness of combined citicoline treatment in patients with mixed dementia and Alzheimer's disease.
[30]
Citicoline & Your Brain | Cognitive Vitality
Jan 4, 2024 · ... stroke or brain injury-related cognitive impairment. Citicoline has ... Typical doses are 250–1,000 mg/day. According to the European ...
[31]
Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic ...
Dec 3, 2020 · Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with ...
[32]
Citicoline in the treatment of Parkinson's disease - PubMed
After 30 days of treatment, the scores on the Columbia rating scale improved 7.3%; rigidity was improved 18.8%; times to walk 10 m and turn over were reduced ...
[33]
Citicoline Uses, Benefits & Dosage - Drugs.com
Oral dosages of 250 to 2,000 mg daily have been evaluated in adolescents and adults in clinical trials. Lower doses (100 mg twice daily) have been used in short ...
[34]
The role of citicoline in cognitive impairment - PubMed Central - NIH
Citicoline's chemical structure. Citicoline inhibits apoptosis associated with cerebral ischemia and several models of neurodegeneration.– It is also able ...
[35]
Citicoline - Uses, Side Effects, and More - WebMD
Citicoline has most often been used by adults in doses of 500-1000 mg by mouth twice daily for up to 12 months. Speak with a healthcare provider to find out ...Overview · Uses & Effectiveness · Possibly Ineffective For
[36]
Citicoline: Uses, Benefits, Dosage, and Side Effects - Healthline
Nov 8, 2023 · The recommended dosage of citicoline as a dietary supplement is 500 milligrams (mg) per day. It's important not to take more than the ...
[37]
A Randomized Efficacy Trial of Citicoline in Patients With Acute ...
The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled ...Missing: COBRIT | Show results with:COBRIT
[38]
Effect of Citicoline on Functional and Cognitive Status Among ...
Nov 21, 2012 · Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive ...<|control11|><|separator|>
[39]
The citicoline brain injury treatment (COBRIT) trial - PubMed - NIH
Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT ...
[40]
Choline-Containing Phospholipids in Stroke Treatment - MDPI
Apr 14, 2023 · Conclusion: Citicoline did not improve the neurological or functional outcomes in acute stroke patients. In contrast, choline alphoscerate ...Missing: mixed | Show results with:mixed
[41]
Citicoline in acute ischemic stroke: A randomized controlled trial
May 31, 2022 · Another updated meta-analysis confirmed these results, as it found a reduction in death or dependency with its use (OR 0.65, 95% CI = 0.54–0.77; ...
[42]
Citicoline Treatment in Acute Ischemic Stroke: A Randomized ...
Jul 12, 2022 · The eight-week treatment with citicoline after acute ischemic stroke may restore intracortical excitability measures, which partially depends on cholinergic ...
[43]
Citicoline for Supporting Memory in Aging Humans
In randomized, placebo-controlled trials of cognitively normal middle-aged and elderly persons, positive effects of citicoline on memory efficacy were found.
[44]
Is Citicoline Effective in Preventing and Slowing Down Dementia?
Jan 12, 2023 · Our results confirm the evidence on the positive effects of citicoline in a wide range of neurological conditions, such as dementia, neuropathic ...
[45]
Role of Citicoline in Patients With Mild Cognitive Impairment - PMC
Feb 16, 2023 · Another study published by Bermejo et al40 suggested that citicoline prevented the development of MCI and dementia in patients who suffered a ...Missing: ADHD depression infarct
[46]
Use of Citicoline in Attention-Deficit/Hyperactivity Disorder - PubMed
Citicoline is an endogenous molecule that has beneficial effects on attention, impulsivity, and memory and is a potential treatment for ADHD.Missing: evidence 2025<|separator|>
[47]
Citicoline Combination Therapy for Major Depressive Disorder
Here, we test citicoline effectiveness as an adjuvant therapy in major depression. Method: A double-blind randomized trial was designed on 50 patients with ...Missing: studies | Show results with:studies
[48]
Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis
Apr 2, 2021 · The results of some recent studies are, however, consistent with the alternative “inside-out” hypothesis according to which MS autoimmunity ...
[49]
Application of Citicoline in Neurological Disorders: A Systematic ...
Oct 12, 2020 · Citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals.
[50]
https://www.aginganddisease.org/EN/10.14336/AD.2022.0913
[51]
https://pmc.ncbi.nlm.nih.gov/articles/PMC9866349/
[52]
Acetylcholine precursor, citicoline (cytidine 5 - PubMed
Citicoline (cytidine 5'-diphosphocholine) is an important precursor for the synthesis of neuronal plasma membrane phospholipids, mainly phosphatidylcholine.
[53]
Metabolism and actions of CDP-choline as an ... - PubMed
Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid ...
[54]
possible new mechanisms of CDP-choline neuroprotection - PubMed
These data suggest multiple beneficial effects of CDP-choline: (1) stabilizing the cell membrane by restoring PtdCho and sphingomyelin (prominent components of ...
[55]
mechanisms of action and effects in ischemic brain injury - PubMed
Membrane repair and regeneration is necessary for recovery from stroke. Furthermore, citicoline may alleviate free fatty acid-induced toxicity which accompanies ...
[56]
Membrane stabilizer: citicoline - PubMed
Citicoline (cytidine-5-diphosphocholine; CDP-choline) is a naturally occurring nucleotide derivative that may reduce central nervous system (CNS) ischaemic ...
[57]
Pivotal role of choline metabolites in remyelination - PubMed
Dec 17, 2014 · We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, ...Missing: Citicoline | Show results with:Citicoline<|separator|>
[58]
Citicoline: neuroprotective mechanisms in cerebral ischemia - PubMed
This review attempts to shed some light on the properties of citicoline that are responsible for its effectiveness. Our studies in transient cerebral ...
[59]
Citicoline: A Superior Form of Choline? - PMC - PubMed Central
Jul 12, 2019 · Citicoline is considered a dietetic source of choline and cytidine. Cytidine does not have any health claim authorized either, but there are claims authorized ...
[60]
Acetylcholine precursor, citicoline (cytidine 5′‐diphosphocholine ...
Dec 16, 2017 · The administration of citicoline serves as a choline donor for the synthesis of acetylcholine. Citicoline has been shown to reduce the ...
[61]
Neuroprotection afforded by prior citicoline administration in ...
Our present findings show novel mechanisms for the neuroprotective effects of citicoline, which cooperate to decrease brain glutamate release after ischemia.
[62]
Neuroprotection and Recovery | Stroke
Dec 16, 2010 · Indeed, we found that citicoline is able to reduce infarct volume in parallel to a decrease in ischemia-induced elevation in brain glutamate ...<|separator|>
[63]
Current knowledge on the neuroprotective and neuroregenerative ...
Oct 1, 2015 · In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood– ...Citicoline · Main Mechanisms Of Action · Neuroprotective Action
[64]
and antidepressant-like effects of citicoline and imipramine in the ...
Citicoline also modulates the quantity of neurotransmitters in the synapses. It increases the level of acetylcholine, dopamine, serotonin, and norepinephrine in ...
[65]
Citicoline - an overview | ScienceDirect Topics
Citicoline demonstrates nearly complete oral absorption, with less than 1% of a radiolabeled dose recovered in feces over five days and oral bioavailability ...
[66]
[PDF] citicoline - goculine - FDA Verification Portal
In clinical use it has been observed to be safe at doses up to. 2g/day. STORAGE CONDITIONS: Store at temperatures not exceeding 30°C. Protect from light. Keep ...
[67]
Plausible use of citicoline as an adjuvant in central nervous system ...
Jun 11, 2024 · Citicoline shows promise as an adjuvant therapy for neurological complications associated with CNS infections.
[68]
Neuroprotective Properties of Citicoline: Facts, Doubts and ...
However, the substance seems to be beneficial in some slowly advancing neurodegenerative disorders such as glaucoma and mild vascular cognitive impairment. This ...
[69]
Citicoline: Uses, Dosage, Side Effects and More | MIMS Philippines
Excretion: Mainly via respiratory CO2 and urine; faeces (<1%). Elimination half-life: 71 hours (urine); 56 hours (respiratory CO2).
[70]
Pharmacokinetics of 14C CDP-choline - PubMed
The absorption, metabolism and excretion of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) were investigated in six adult healthy subjects.Missing: half- life
[71]
[PDF] strolin - Torrent Pharmaceuticals
... citicoline elimination occurs mainly via respiratory CO2 and urinary excretion ... elimination half-life is 56 hours for CO2 and 71 hours for urinary excretion.<|separator|>
[72]
SCARLET (Supplemental Citicoline Administration to Reduce Lung ...
The elimination half-life for CDP-choline that is not incorporated into phospholipids is rapid (56 h for CO2 and 71 h for urinary excretion). Hence, it is ...
[73]
[PDF] World Journal of Pharmaceutical and Life Sciences
Oct 11, 2023 · Pharmacokinetics: Citicoline is water−soluble, with more than 90 ... steady state plasma concentrations are achieved within 3 days of dosing.[20].
[74]
Citicoline for treating people with acute ischemic stroke - PMC
Since 17 April 2009, citicoline has been banned in the USA and Canada (Chen 2016; FDA 2019). Conducting a systematic review according to Cochrane methodology is ...
[75]
[PDF] PATIENT INFORMATION LEAFLET CITICOLINE TABLETS 500 mg ...
Dosage adjustment is required in those with mild-to-moderate renal impairment and in the elderly population with diminished renal function.Missing: monitoring | Show results with:monitoring<|control11|><|separator|>
[76]
The synthesis of cytidine diphosphate choline, cytidine ... - PubMed
The synthesis of cytidine diphosphate choline, cytidine diphosphate ethanolamine, and related compounds. J Biol Chem. 1956 Sep;222(1):185-91.Missing: citicoline | Show results with:citicoline
[77]
Citicoline - an overview | ScienceDirect Topics
Citicoline provides the brain with a source of choline and cytidine, which are efficiently used in the Kennedy cycle to generate phospholipids. Although choline ...
[78]
A process for preparing pure citicoline (cdp-choline) - Google Patents
Sep 6, 2013 · 3,803,125 discloses a process for preparing citicoline by reacting morpholidiate cytidine 5 '-monophosphate with calcium phosporyl choline ...
[79]
https://www.torrentpharma.com/assets/108_66d33f0903.pdf
[80]
Citicoline sodium synthesis - ChemicalBook
Synthesis of Citicoline sodium from Cytidine 5'-Diphosphocholine.Chemicalbook can provide 7 synthetic routes.
[81]
Method for synthesizing citicoline sodium by using cytidine ...
The earliest enzyme-catalyzed synthesis method is to synthesize citicoline sodium by catalyzing Cytidine Triphosphate (CTP) and phosphorylcholine with ...
[82]
Preparation method of Citicoline Sodium
Nov 20, 2024 · Preparation method of Citicoline Sodium · 1. Preparation of Cytidine and CMP (Cytidine Monophosphate): · 2. Reaction with Choline: · 3. Formation ...
[83]
From yeast to humans – roles of the Kennedy pathway ... - FEBS Press
Nov 27, 2017 · The main pathway for the synthesis of PC is the Kennedy (CDP-choline) pathway. In this pathway, choline is converted to phosphocholine by choline kinase.PC synthesis: Insights from yeast · The Kennedy pathway · CTP:phosphocholine...
[84]
Phosphatidylcholine and the CDP-Choline Cycle - PMC - NIH
The CK is the first committed step in the CDP-choline pathway of PtdCho synthesis and its regulation has been investigated in cultured mammalian cells.
[85]
https://patents.google.com/patent/WO2013128393A1/en