Cytidine 5'-Diphosphocholine Chemical Properties

Melting point:

>185°C (dec.)

alpha 

D25 +19.0° (c = 0.86 in H2O)

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

Water (Sparingly)

pka

4.4(at 25℃)

form 

Solid

color 

White

Stability:

Moisture Sensitive

InChIKey

RZZPDXZPRHQOCG-APGYLPRWNA-N

SMILES

O[C@@H]1[C@@H]([C@@H](COP(O)(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C=CC(N)=NC1=O)O |&1:1,2,3,21,r|

LogP

-7.070 (est)

CAS DataBase Reference

987-78-0(CAS DataBase Reference)

Safety Information

Toxicity

LD50 in mice, rats (mg/kg): 4600 ±335, 4150 ±370 i.v.; both species 8 g/kg orally (Grau)

Cytidine 5'-Diphosphocholine Usage And Synthesis

Description

Citicoline whose chemical name choline cytosine nucleoside-5'-diphosphate monosodium salt, is a precursor for lecithin biosynthesis, and when brain function declines, the content of lecithin in brain tissue is significantly reduced.

Originator

Nicholin,Cyanamid,Italy,1971

Uses

Cytidine 5'-Diphosphocholine is used as antidepressant, 5HT uptake inhibitor.

Definition

ChEBI: CDP-choline is a member of the class of phosphocholines that is the chloine ester of CDP. It is an intermediate obtained in the biosynthetic pathway of structural phospholipids in cell membranes. It has a role as a human metabolite, a psychotropic drug, a neuroprotective agent, a Saccharomyces cerevisiae metabolite and a mouse metabolite. It is a member of phosphocholines and a member of nucleotide-(amino alcohol)s. It is functionally related to a CDP. It is a conjugate base of a CDP-choline(1+).

Manufacturing Process

A 250 ml conical flask containing 30 ml of a reaction liquor (pH 7.0) having a composition of 7.38 mg/ml of disodium salt of CMP (cytidine-5'- monophosphate), 24 mg/ml of choline, 10 mg/ml of glucose, 100 mg/ml of acetone-dried cells of Brevibacterium ammoniagenes ATCC 6872, 11.6 mg/ml of monopotassium phosphate, 20 mg/ml of dipotassium phosphate and 2.96 mg/ml of magnesium sulfate, (MgSO4·7H2O), was subjected to culturing at 30°C for 4 hours. Cytidine diphosphate choline was formed and accumulated at a concentration of 3.8 mg/ml in the culture liquor.
The pH of 1.2 liters of filtrate containing 3.8 mg/ml of cytidine diphosphate choline, obtained by removing solid matters from the culturing liquor, was adjusted to a pH of 8.5 with a 0.5 N KOH solution. The filtrate was passed through a column of strongly basic anion exchange resin, Dowex 1 x 2 (formic acid type). After washing the resin with water, a formic acid solution was passed through the column with gradual increase in the concentration of formic acid (until 0.04 N max.). A fraction of cytidine diphosphate choline was collected by elution according to the so-called gradient elution method and absorbed onto carbon powders. Then, elution was effected with acetone, and the eluate was concentrated and dried. 1.3 g of cytidine diphosphate choline (Cytidine 5'-Diphosphocholine) powders were obtained.

Therapeutic Function

Cerebral circulation stimulant

benefits

Citicoline (CDP-choline; Cytidine 5'-Diphosphocholine), a naturally occurring endogenous compound, is an essential intermediate in the biosynthesis of cell membrane phospholipids. Produced endogenously, citicoline serves as a choline donor in the metabolic pathways for the biosynthesis of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. When a citicoline supplement is taken by mouth or intravenously, its two main components, cytidine and choline, are fully absorbed into the bloodstream. Once absorbed, citicoline is widely distributed throughout the body and can cross the blood-brain barrier and reach the central nervous system (CNS), where it is incorporated into phospholipids. Citicoline activates the biosynthesis of structural phospholipids that form neuronal membranes, increases brain metabolism, and influences levels of multiple neurotransmitters. Citicoline has increased acetylcholine, norepinephrine and dopamine levels in the central nervous system. Citicoline has been proposed to protect nerve cells after cerebral ischemia. In animal studies, it has been found to improve learning and memory. Citicoline may be used as a treatment for cerebral vascular disease after head trauma and cognitive impairment arising from multiple causes. Citicoline helps recovery from post-traumatic coma and neurological deficits in those who have had an ischemic cerebral vascular disease such as stroke. Additional uses of citicoline include treatment of age-related cognitive decline and degenerative neurological diseases such as Alzheimer's disease.

Mechanism of action

Cytidine 5'-Diphosphocholine may have neuroprotective effects due to its preservation of cardiolipin and sphingomyelin, preservation of arachidonic acid content of phosphatidylcholine and phosphatidylethanolamine, partial restoration of phosphatidylcholine levels, and stimulation of glutathione synthesis and glutathione reductase activity. It's effects may also be explained by the reduction of phospholipase A2 activity. Citicoline increases phosphatidylcholine synthesis.

Side effects

Citicoline has a very low toxicity profile in animals and humans. Minor transient adverse effects are rare and most commonly include stomach pain and diarrhea.

References

[1] Journal of Chemical Research, 2016, vol. 40, # 6, p. 358 - 360
[2] Patent: CN105732752, 2016, A. Location in patent: Paragraph 0014; 0016; 0019

Cytidine 5'-Diphosphocholine(987-78-0)Related Product Information

• ASIALOGANGLIOSIDE-GM1
• Cytidine 5'-diphosphate trisodium salt
• CHOLINE
• Sulbactum Sodium
• Cytidine
• Choline hydroxide
• Cytosine
• phosphorylcholine
• CYTIDINE 5'-DIPHOSPHOCHOLINE SODIUM SALT DIHYDRATE
• CYTIDINE 5'-DIPHOSPHOCHOLINE
• Citicoline sodium
• CYTIDINE 5'-DIPHOSPHO[METHYL-14C]CHOLINE, AMMONIUM SALT
• CYTIDINE DIPHOSPHOCHOLINE [METHYL 3H]
• CYTIDINE 5'-DIPHOSPHOCHOLINE, DISODIUM SALT, [5-3H]-