title: Neuroprotective properties of citicoline: facts, doubts and unresolved issues.
abstract: Citicoline is the generic name of the pharmaceutical substance that chemically is cytidine-5'-diphosphocholine (CDP-choline), which is identical to the natural intracellular precursor of phospholipid phosphatidylcholine. Following injection or ingestion, citicoline is believed to undergo quick hydrolysis and dephosphorylation to yield cytidine and choline, which then enter the brain separately and are used to resynthesize CDP-choline inside brain cells. Neuroprotective activity of citicoline has been repeatedly shown in preclinical models of brain ischaemia and trauma, but two recent, large, pivotal clinical trials have revealed no benefits in ischaemic stroke and traumatic brain injury. However, the substance seems to be beneficial in some slowly advancing neurodegenerative disorders such as glaucoma and mild vascular cognitive impairment. This paper critically discusses issues related to the clinical pharmacology of citicoline, including its pharmacokinetics/biotransformation and pharmacodynamics/mode of action. It is concluded that at present, there is no adequate description of the mechanism(s) of the pharmacological actions of this substance. The possibility should be considered and tested that, in spite of apparently fast catabolism, the intact citicoline molecule or the phosphorylated intermediate products of its hydrolysis, cytidine monophosphate and phosphocholine, are pharmacologically active.
authors: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106, Warsaw, Poland, pgrieb@imdik.pan.pl.
authors: Pawel
authors: P
authors: Grieb
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy; D002545:Brain Ischemia / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003566:Cytidine Diphosphate Choline / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D003566:Cytidine Diphosphate Choline