Cytidine 5'-Diphosphocholine

Originator

Nicholin,Cyanamid,Italy,1971

The Uses of Cytidine 5'-Diphosphocholine

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

Background

Citicoline is a donor of choline in biosynthesis of choline-containing phosphoglycerides. It has been investigated for the treatment, supportive care, and diagnosis of Mania, Stroke, Hypomania, Cocaine Abuse, and Bipolar Disorder, among others.

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 powders were obtained.

Therapeutic Function

Cerebral circulation stimulant

Metabolism

Not Available