Pharmacology Pharmacodynamics Citicoline is a complex organic molecule that functions as an intermediate in the biosynthesis of cell membrane phospholipids. Citicoline iscomposed of two essential moieties, cystidine and choline, linked by a diphosphate bridge, and serves as the phosphocholine donor to 1, 2-diacylglycerol DAG to form phosphatidylcholine. The extensive damage caused by stroke requires repair and regeneration of the axons and synapses of neurons, so new membrane production is necessary. The brain uses choline preferentially for acetylcholine synthesis, which can limit the amount of choline available for phosphatidylcholine production. When the demand for acetylcholine increases or choline stores in the brain are low, phospholipids in the neuronal membrane can be catabolized to supply the needed choline.
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Corresponding author. This article has been cited by other articles in PMC. 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. 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.
Key Points for Decision Makers Citicoline is chemically identical to CDP-choline, the natural precursor of the major cell membrane phospholipid phosphatidylcholine. Given orally or by injection, citicoline is non-toxic and very well tolerated.
Preclinical experiments with various models of central neurodegenerative diseases have shown that citicoline displays significant neuroprotective properties. However, recent large and well-controlled data have shown no benefit from citicoline in acute ischaemic stroke and traumatic brain injury. The pharmacological actions of citicoline in the central nervous system seem to be pleiotropic and involve, amongst other things, modulation of some kinases and sirtuin However, our understanding of the mechanisms involved is, at most, fragmentary.
The work of Kennedy and collaborators in the s showed that this phosphorylated choline nucleotide is a precursor of glycerophospholipid phosphatidylcholine PC [ 1 ]. PC and its twin compound phosphatidylethanolamine PEt are the two most abundant phospholipids in eukaryotic cells, accounting for more than half of the total phospholipid content in membranes.
These enzymes are located intracellularly, in the endoplasmic reticulum and cell nucleus [ 3 ]. Choline that is used for synthesis of phosphatidylcholine through the CDP-choline pathway is derived from transport of exogenous choline into the cell or from phospholipase D-mediated turnover of PC [ 4 ].
Neuroprotective Properties of Citicoline: Facts, Doubts and Unresolved Issues
Please note that this medicine may be available in various strengths for each active ingredient listed above. Please consult with your doctor for case-specific recommendations. Is Citicoline Injection safe while breastfeeding? Please discuss the risks and benefits with your doctor. Can Citicoline Injection be used for treatment of head trauma and improvement of neurological functions in patients with ischemic strokes?
Do not take this medicine in higher amounts or frequency than that told by your doctor. Do not drive or do anything that requires mental focus until you know how it affects you. Inform your doctor if you develop allergic reaction after taking the medication. Side effects such as trouble sleeping, diarrhoea, stomach pain, decreased blood pressure, irregular heart rate may occur with Citicoline. These may not be with everyone.