CDP choline

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Structural formula
Structure of CDP choline
General
Surname CDP choline
other names
  • Cytidine-5'-diphosphocholine
  • Citicoline
  • [(2 R , 3 S , 4 R , 5 R ) -5- (4-Amino-2-oxopyrimidin-1-yl) -3,4-dihydroxyoxolan-2-yl] methyl- {oxido- [2- ( trimethylazaniumyl) ethoxy] phosphoryl} phosphate ( IUPAC )
Molecular formula C 14 H 26 N 4 O 11 P 2
External identifiers / databases
CAS number
  • 987-78-0
  • 1256-10-6 (cation)
EC number 213-580-7
ECHA InfoCard 100.012.346
PubChem 13804
Wikidata Q28529682
Drug information
ATC code

V06 DX50

properties
Molar mass 487.32 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

CDP-choline is a nucleoside diphosphate with the base cytosine , which is linked to choline via a phosphoric acid ester . CDP-choline is water-soluble and has a very good bioavailability (> 90%).

Effect in the body

CDP-choline is an intermediate product of the cell membrane metabolism, which is required as an essential component for the biosynthesis of cell membrane phospholipids (phosphatidylcholine, also: lecithin). CDP-choline is synthesized endogenously and represents the limiting step in phosphatidylcholine synthesis, the most important metabolic step for the construction and repair of cell membranes.

Pharmacokinetic studies in healthy adults showed that orally administered CDP-choline is absorbed very quickly and less than 1% is excreted enterally. Exogenously applied CDP-choline is hydrolyzed in the intestinal wall and in the liver and absorbed as choline and cytidine. Choline and cytidine are then further metabolized, passing the blood-brain barrier, among other things, to be resynthesized in the brain into CDP-choline. Pharmacokinetic studies show that respiratory excretion via the lungs and urine is biphasic, analogous to plasma availability.

Cytidine, an important component of nucleic acids (DNA / RNA), is cytoplasmic converted into cytidine triphosphate (CTP). In the CDP-choline metabolism, choline is phosphorylated by the enzyme choline kinase. In the subsequent reaction, the product phosphorylcholine is converted to CDP-choline by the enzyme CTP-phosphocholine-cytidine transferase (CCT) with CTP with cleavage of a pyrophosphate group. In the last step, catalyzed by the enzyme choline phosphotransferase, CDP-choline reacts with diacylglycerol to form phosphatidylcholine.

In animal experiments, treatment with 500 mg / kg body weight / day for 90 days showed an increase in the phosphatidylcholine level by 25%, the phosphatidylethanolamine level by 17%, and the phosphatidylserine level by 42%. Choline and cytidine, the main metabolites of CDP-choline, can already be detected after a single oral dose of CDP-choline through significantly increased plasma levels in young and elderly patients. MR-spectroscopic investigations have shown that treatment with CDP-choline for weeks in elderly people significantly increases the plasma levels of phosphodiesters, by-products of phospholipid metabolism, in the brain. A CDP-choline treatment thus increases the phospholipid synthesis as well as the turnover. CDP-choline has been shown to be very safe in toxicological tests, showing no significant systemic cholinergic effects.

Areas of application

Due to its mode of action, CDP-choline was associated with regenerative functions in traumatic and degenerative brain diseases early on. Exogenously administered CDP-choline has been investigated in more than 11,000 patients in clinical studies (stroke, traumatic brain injury, dementia). The effects of CDP-choline after an (ischemic or hemorrhagic) stroke have been particularly well deciphered: anti-excitatory, anti-oxidative, membrane-stabilizing and regenerative effects are described. Clinical studies showed the first indications of a reduction in the infarct volume and neurological deficit after CDP-choline treatment in stroke patients. A pooled data analysis of the effectiveness of CDP-choline in patients with acute ischemic stroke showed that more than every fourth patient treated with CDP-choline showed a largely complete recovery after three months ( NIHSS value ≤ 1, Barthel index ≥ 95 plus mRS value ≤ 1). In addition, a Cochrane review of the pooled data from all seven double-blind and placebo-controlled studies on ischemic stroke confirms the effectiveness of CDP-choline. The likelihood of avoiding mortality / disability in long-term follow-up was clearly in favor of CDP-choline. Not least because of this data, CDP-Choline has been used for stroke treatment worldwide for over 30 years. a. in Europe, Latin America and Asia. According to strict evidence-based criteria, however, there is currently no proof of effectiveness from a multi-center phase III study, which is currently being conducted in an international phase III study (ICTUS; International Citicholin Trial in Acute Stroke). This study was discontinued in 2011 because there were no significant differences in the improvement in disease symptoms in the two participating groups (verum versus placebo). As a result of the study, citicoline was found to be ineffective in treating mild and moderate ischemic strokes.

Other areas of application discussed include cognitive disorders of various origins, e. B. dementia, Parkinson's disease, drug addiction, alcoholism, amblyopia and glaucoma, as well as protection of the endothelial cell membranes in the event of complications after infectious diseases such as sepsis or cerebral malaria.

Trade names and dosage forms: Ceraxon® 500 mg, Trommsdorff GmbH & Co. KG Arzneimittel. Trommsdorff withdrew the product from the market on August 1, 2014. Since March 2015 it has been on the market again in Germany as Citicoline CDP Choline from Jarrow Deutschland GmbH with 250 mg per capsule. There are also dealers such as GHirn UG who offer products with citicoline.

See also

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Choline Metabolism  - Learning and Teaching Materials
Wikibooks: Biochemistry and Pathobiochemistry: Phosphoglyceride Metabolism  - Learning and Teaching Materials

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ a b Entry on CDP-choline in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on November 28, 2018.
  3. ↑ a b W. R. Schäbitz: CDP choline for the treatment of stroke. In: Psychopharmacology. 3, 2009, pp. 101-105.
  4. ↑ A. Davalos, J. Castillo, J. Alvarez-Sabin et al .: Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. In: Stroke. 33, 2002, pp. 2850-2857.
  5. ↑ AM Rao, JF Hatcher, RJ Dempsey: CDP-choline: neuroprotection in transient forebrain ischemia of gerbils. In: J Neurosci Res. 58, 1999, pp. 697-705.
  6. ↑ JR Dinsdale, GK Griffiths, C. Rowlands et al: Pharmacokinetics of 14C CDP-choline. In: drug research. 33, 1983, pp. 1066-1070.
  7. ↑ IL G-Coviella, RJ Wurtman: Enhancement by cytidine of membrane phospholipid synthesis. In: J Neurochem. 59 (1), 1992, pp. 338-343.
  8. ↑ KJ D'Orlando, BW Sandage Jr .: Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury. In: Neurol Res. 17, 1995, pp. 281-284.
  9. ↑ I. Lopez-Coviella, J. Agut, V. Savci include: Evidence did 5'-cytidinediphosphocholine can affect brain phospholipid composition by Increasing choline and cytidine plasma levels. In: J Neurochem. 65, 1995, pp. 889-894.
  10. ↑ SM Babb, LL Wald, BM Cohen et al: Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. In. Psychopharmacology. (Berl)
  11. ↑ a b J. J. Secades, JL Lorenzo: Citicoline: pharmacological and clinical review, update of 2006. In: Methods Find Exp Clin Pharmacol. 28 (Suppl B), 2006, pp. 1-56.
  12. ^ WR Schäbitz et al: The effects of prolonged treatment with citicoline in temporary experimental focal ischemia. In: J Neurol Sci. 138, 1996, pp. 21-25.
  13. ↑ JL Saver: 27th ISC, San Antonio, Texas 2002.
  14. ↑ A. Dávalos include: Citicoline in the treatment of acute ischemic stroke: an international, randomized, multicentre, placebo-controlled study (ICTUS trial). In: The Lancet . 380 (9839), Jul 28, 2012, pp. 349-357. doi: 10.1016 / S0140-6736 (12) 60813-7 .
  15. ↑ R. Jambou, F. El-Assaad, V. Combes, GE Gray: Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases. In. Int J Biochem Cell Biol. 1 (7), 2009, pp. 1467-1470. Epub February 23, 2009.
  16. ↑ ABDATA pharmaceutical data service of the advertising and sales company of German pharmacists.