The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives

Abstract

BackgroundCiticoline is able to potentiate neuroplasticity and is a natural precursor of phospholipid synthesis, or rather serves as a choline source in the metabolic pathways for biosynthesis of acetylcholine. Several studies have shown that it can have beneficial effects both in degenerative and in vascular cognitive decline. The aim of the present study was to review the pharmacokinetics and pharmacodynamics of this drug and its role in cognitive impairment according to the present medical literature.MethodsA MEDLINE® search was made using the following key words: citicoline, pharmacokinetics, pharmacodynamics, elderly, cognitive impairment, vascular dementia, and Alzheimer’s disease. Recent studies on the possible role of citicoline in increasing sirtuin 1 (SIRT1) expression were assessed. Some personal studies were also considered, such as the VITA study and the IDEALE study.ResultsAdministered by both oral and intravenous routes, citicoline is converted into two major circulating metabolites, cytidine and choline. It is metabolized in the gut wall and liver. Pharmacokinetic studies suggested that it is well absorbed and highly bioavailable with oral dosing. A number of studies have clearly shown the possible role of citicoline in cognitive impairment of diverse etiology. It can also modulate the activity/expression of some protein kinases involved in neuronal death and increases SIRT1 expression in the central nervous system. The VITA study and the IDEALE study suggested that both parenteral and oral citicoline are effective and safe. Other studies have clearly demonstrated citicoline’s effects on several cognitive domains. Conversely, some studies did not point out any evidence of efficacy of this drug.ConclusionCiticoline appears to be a promising agent to improve cognitive impairment, especially of vascular origin. In fact, so far it appears as a drug with the ability to promote “safe” neuroprotection, capable of enhancing endogenous protective. Large clinical trials are needed to confirm its benefits.

Citicoline as Add-On Treatment in Alzheimer’s Disease: Tips from the Citicholinage Study

“…Combined treatment was safe and well tolerated, with no differences vs. the AchEIs alone (restlessness, headache, gastric intolerance) and as reported in the literature they were self-limiting [6]. No significant systemic cholinergic effects following the use of citicoline have ever been reported.…”

“…The combination treatment of CDP-choline (or citicoline) with AchEIs in AD seems to prolong their beneficial effects, probably through an increase in acetylcholine intrasynaptic levels and the possible actions on phospholipid synthesis, chiefly phosphatidylcholine, cellular function and neuronal repair, in particular for its actions on neurogenesis, synaptogenesis, gliagenesis and angiogenesis [7,8] (included the restoration of mitochondrial ATPase and membrane Na + /K + ATPase activity and the inhibition of phospholipase A 2 activity) [6]. Mostly it works as a choline source for the biosynthesis of acetylcholine [1][2][3].…”

The assessment of the efficacy of citicoline in the early and recovery stages of stroke

“…В ряде исследований [25][26][27] продемонстрировано нейропротективное действие цитиколина в остром и раннем восстановительном периодах инсульта, сопровожда-Журнал неврологии и психиатрии, 6,2016 обзоры ющемся КН. Н.В.…”

Comparative Oral Absorption of Different Citicoline and Homotaurine Formulations: A Single-Dose, Two-Period Crossover Trial in the Dog

“…The effects attributed to citicoline include antiapoptotic effects, neurotrophic properties, protection after partial optic nerve crush, reduction of excitotoxicity, effects on nonglutamatergic neurotransmitter systems, and effects on remyelination [5]. In addition, citicoline appears to be a promising agent for the improvement of cognitive impairment [6].…”