Citicoline
Citicoline (Cytidine 5’-diphosphocholine or CDP-choline), a naturally-occurring endogenous nucleoside, is an intermediate compound in the major pathway for the biosynthesis of the structural phospholipids of cell membranes, including neurons. This pathway is termed the Kennedy pathway.
Chemistry
Citicoline is a polarized molecule with a molecular weight of 488.33. It is a white crystalline, very hygroscopic powder which is soluble in water.
Pharmacodynamics
When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the body, cross the blood-brain barrier, and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the cellular membrane and microsomes.
The concept that administration of exogenous Citicoline might augment the synthesis of neural membrane phospholipid is attractive, because accelerated replacement or repair plays a critical role in maintaining the healthy function of numerous physiological processes. It has shown therapeutic efficacy in a variety of diseases in which membrane disorder, dysfunction, or degeneration result in cellular and tissue ischaemia and necrosis.
Pharmacology
Citicoline activates the biosynthesis of structural phospholipids in the neuronal membrane, increases cerebral metabolism, and increases the levels of various neurotransmitters, including acetylcholine and dopamine. Citicoline has shown neuroprotective effects in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that Citicoline restores the activity of mitochondrial ATPase and of membrane Na+ /K+ATPase, inhibits the activation of phospholipase A2 and accelerates the re-absorption of cerebral edema in various experimental models.
Therapeutic Uses
It is suggested that Citicoline may be suitable for the following conditions:
Cerebrovascular disease—e.g. from ischaemia due to stroke, where Citicoline accelerates the recovery of consciousness and overcoming motor deficit. The clinical testing of Citicoline has challenged the historical concept that one can do nothing for a stroke patient after a certain period of time has transpired after the onset of symptoms. The practicality of a drug that can beadministered up to 24 hours after stroke is a key factor in evaluating the potential of Citicoline.
The result of a recent phase 3 clinical trial among patients suffering from ischaemic stroke demonstrated a statistically and clinically significant improvement in the neurological function of patients treated with the optimal dose of Citicoline, 500 mg daily. The potential of Citicoline as a stroke therapy is underscored by other key attributes: its oral dosage form, a 24 hour window of therapeutic opportunity following stroke, and an apparent absence of significant side-effects. Preliminary evidence suggests that in a small sub-group of patients, Citicoline may reduce the size of the impact caused by stroke.
Head trauma of varying severity—In a clinical trial, Citicoline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced hospital stay.
Cognitive disorders of diverse etiology—e.g. senile cognitive impairment which is secondary to degenerative diseases (e.g. Alzheimer’s disease) and to chronic cerebral vascular disease. Citicoline improves scores on cognitive evaluation scales and slowed the progression of Alzheimer’s disease.
Parkinson’s disease—Citicoline has also been shown to be effective as co-therapy for Parkinson’s disease. Beneficial neuroendocrine, neuroimmunomodulatory, and neurophysiological effects have been described. Considerable experimental evidence of effects of Citicoline on CNS dopaminergic systems has accumulated. After treatment with Citicoline, regeneration of cells in rats with substantia nigra lesions has been demonstrated. Citicoline increases striatal dophamine and tyrosine hydroxylase synthesis.
Safety
Citicoline is a safe and effective nutraceutical, and toxicological tests have shown no serious side effects even after prolonged treatment.
References
[1] Secades, J.J. and Frontera, G. CDP-choline: Pharmaceutical and clinical review. Methods Find Exp Clin Pharmacol. 1995;17 Suppl B:1-54. [Abstract]
[2] Weiss, G.B. Metabolism and actions of CDP-Choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-660. [Abstract]
[3] G-Coviella, I.L. and Wurtman, R.J. Enhancement by cytidine of membrane phospholipid synthesis. J Neurochem. 1992;59(1):338-343. [Abstract]
[4] Spiers, P.A. et al. Citicoline improves verbal memory in aging. Arch Neurol. 1996;53(10):411-418. [Abstract]
[5] Alvarez, X.A. et al. Citicoline improves memory performance in elderly subjects. Method Find Exp Clin Pharmacol. 1997;19(3):201-210. [Abstract]
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