Citicoline acts as a choline donor in the biosynthesis of the neurotransmitter acetylcholine and as an intermediate in phosphatidylcholine synthesis. By providing choline for acetylcholine synthesis, it supports cholinergic neurotransmission. Citicoline also inhibits ROS production and apoptosis, contributing to its neuroprotective effects. It increases the levels of acetylcholine, norepinephrine, and dopamine in the central nervous system.

Retinal cells were subjected to escalating doses of either homotaurine or citicoline for a full day in order to assess the possible neuroprotective effects of the compounds. The effects of homotaurine or cocaine at concentrations of 1 μM, 10 μM, and 100 μM on retinal cell viability were examined. In cultures treated with citicoline or homotaurine, retinal cells were effectively preserved; there was no sign of toxicity or appreciable loss of viability following treatment. In vitro, homotaurine at 100 μM is an effective concentration to increase neuroprotection in experimental glaucoma models, whereas cocaine at 100 μM does not injure retinal glial cells. As a result, this homotaurine and citicoline concentration was utilized in all ensuing investigations. Retinal cell cultures were treated to citicoline 24 hours prior to glutamate treatment in order to assess whether combined treatment with citicoline and homotaurine can generate synergistic neuroprotection against glutamate excitotoxicity. 100 μM for base, 100 μM for homotaurine, and 100 μM for citicoline with homotaurine. A notable rise in cell viability was noted in the presence of 100 μM citicoline [1].
Citicoline inhibits reactive oxygen species (ROS) and apoptosis in vitro. It promotes the synthesis of phosphatidylcholine and supports cell membrane integrity. The compound has been shown to have protective effects in neuronal cell cultures against oxidative stress and excitotoxicity. It also increases acetylcholine levels in neuronal cells.

The tonic phase thresholds for clonic and lethal seizures were more significantly elevated (18.54% and 50.08%, respectively, compared to controls) when citicoline at a dose of 1000 mg/kg was administered. After injecting 1000 mg/kg of citicoline, the anticonvulsant action becomes most noticeable [2].
In vivo, citicoline has been investigated for the treatment of stroke, mania, cocaine abuse, and bipolar disorder. Administration at a dose of 1000 mg/kg produces a pronounced increase in the threshold of clonic seizures and the tonic phase of seizures with lethal outcome in animal models. It demonstrates protective effects in cerebral ischemia, traumatic brain injury, and memory disorders.

In vitro assays for citicoline typically measure the incorporation of choline into phosphatidylcholine. Cells are treated with citicoline, and the synthesis of phosphatidylcholine is measured using radiolabeled precursors. Acetylcholine levels may be measured by HPLC or enzymatic assays. ROS production is measured using fluorescent probes such as DCFH-DA. Apoptosis is assessed by caspase activity assays or Annexin V staining.

Cellular assays for citicoline are performed using neuronal cell lines (e.g., SH-SY5Y, PC12) or primary neurons. Cells are treated with citicoline at concentrations ranging from 10 to 1000 μM for 24-72 hours. Cell viability is assessed using MTT or LDH release assays. ROS production is measured using fluorescent probes. Apoptosis is assessed by flow cytometry using Annexin V staining or by caspase activity assays.

In vivo animal studies with citicoline are conducted in rodent models of cerebral ischemia, traumatic brain injury, and epilepsy. In the seizure model, citicoline is administered at doses of 1000 mg/kg, and seizure threshold is measured. In cerebral ischemia models, neurological deficits and infarct size are assessed.

Citicoline is well absorbed and is metabolized to cytidine and choline, which cross the blood-brain barrier. It is an endogenous compound, and its pharmacokinetics follow normal metabolic pathways. The compound is primarily excreted as carbon dioxide and urine. Its half-life is short. For research use, it is typically dissolved in water or saline.

Citicoline is generally well tolerated with a favorable safety profile. It is an endogenous compound and is not associated with significant toxicity at therapeutic doses. Side effects are mild and include gastrointestinal discomfort and headache. The compound has been used extensively in clinical research and is considered safe for human use.

[1]. Cytoprotective Effects of Citicoline and Homotaurine against Glutamate and High Glucose Neurotoxicity in Primary Cultured Retinal Cells. Oxid Med Cell Longev. 2017;2017:2825703.

[2]. Increase of the seizure threshold in C57BL/6 mice after citicoline administration. Bull Exp Biol Med. 2015 Jan;158(3):315-7.

Citicoline (CDP-choline) is a phosphate-choline compound and the chlorinated ester of citicoline (CDP). It is an intermediate in the biosynthesis of phospholipids in cell membrane structures. Citicoline has applications in human metabolism, psychotropic drugs, neuroprotective agents, Saccharomyces cerevisiae metabolism, and mouse metabolism. It belongs to the phosphate-choline class of compounds and the nucleotide-(amino alcohol) class of compounds. Its function is related to citicoline (CDP). It is the conjugate base of citicoline (CDP-choline). Citicoline is the choline donor in the biosynthesis of choline-containing glycerophosphates. Nicotinic acid has been studied for the treatment, supportive care, and diagnosis of mania, stroke, hypomania, cocaine abuse, and bipolar disorder. Nicotinic acid has been reported in fruit flies, humans, and other organisms with relevant data. Citicoline is a nutritional supplement rich in choline and cytidine, with potential neuroprotective and nootropic effects. Citicoline, also known as cytidine-5-bisphosphate choline or CDP-choline, is hydrolyzed in the intestine to cytidine and choline. After absorption, both cytidine and choline are dispersed, participating in various biosynthetic pathways and crossing the blood-brain barrier to be resynthesized as citicoline in the brain. Citicoline is the rate-limiting product of phosphatidylcholine synthesis. This drug can also increase the levels of acetylcholine (Ach), norepinephrine (NE), and dopamine in the central nervous system (CNS). Furthermore, citicoline participates in the preservation of sphingomyelin and cardiolipin, as well as the restoration of Na+/K+-ATPase activity. Citicoline can also increase glutathione synthesis and glutathione reductase activity, and exert anti-apoptotic effects. Choline donors participate in the biosynthesis of choline-containing glycerophosphates. See also: Citicoline sodium (note moved to).
Citicoline is a neuroprotective agent and nutritional supplement used for the treatment of stroke, traumatic brain injury, and neurodegenerative disorders. It is also used to enhance memory and cognitive function. The compound is available as a dietary supplement and has been studied in numerous clinical trials. It is not approved by the FDA as a drug but is widely used as a supplement in many countries.

C14H26N4O11P2

488.32

488.107

987-78-0

Citicoline sodium;33818-15-4

13804

White to off-white solid powder

851.4ºC at 760 mmHg

-7.07

4

11

10

31

821

4

C[N+](C)(C)CCOP(=O)([O-])OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=CC(=NC2=O)N)O)O

RZZPDXZPRHQOCG-OJAKKHQRSA-N

InChI=1S/C14H26N4O11P2/c1-18(2,3)6-7-26-30(22,23)29-31(24,25)27-8-9-11(19)12(20)13(28-9)17-5-4-10(15)16-14(17)21/h4-5,9,11-13,19-20H,6-8H2,1-3H3,(H3-,15,16,21,22,23,24,25)/t9-,11-,12-,13-/m1/s1

[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] 2-(trimethylazaniumyl)ethyl phosphate

Cdp-choline; Cytidine 5-diphosphocholine; Citicoline

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~50 mg/mL (~102.39 mM)
DMSO : ~1 mg/mL (~2.05 mM)

Solubility in Formulation 1: 50 mg/mL (102.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)