Citicoline used, Side effects, Dose, & more

 Citicoline

Brand name:- Citilin, Citinova 500mg tab, 500mg/2ml injection., Strolin 500mg tab, Strocit, Ceham ,Citistar.

Citicoline, also known as cytidine diphosphate-choline or cytidine 5 '-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is naturally occurring in the cells of human and animal tissue, in particular the organs. 

Pharmacodynamic:- 

Citicoline increased choline acetyltransferase expression for phosphatidylcholine synthesis after hypoglycemia. These findings suggest that neuronal membrane stabilization by citicoline administration can save neurons from the degeneration process after hypoglycemia, as seen in several ischemia studies.

Pharmacokinetics:- 

Administration of 300mg dose to healthy adults shows nearly complete absorption, with less than 1% of excretion in feces . The main route of excretion was found to be via a respiratory route, with significant excretion occurring through urine. A confirmatory study, using radioactive Citicoline in rats, found 62.8% of total radioactivity distributed in brain tissues as phospholipids, including phosphatidylcholine and sphingomyelin. Metabolites of orally administered Citicoline resynthesize endogenous Citicoline, which yields beneficial effects for the synthesis and incorporation of neuronal phospholipids . Only a small percentage of total Citicoline crosses the BBB as choline and Cytidine, the utilization of these precursors is extremely efficient 

Mechanism of action:- 

Citicoline has beneficial effects on neurological functions; it acts by increasing the synthesis of phosphatidylcholine, the primary neuronal phospholipid and enhancing the production of acetylcholine . Brain phospholipid synthesis is impaired following stroke and ischemic events. Oral citicoline administration increases the plasma levels of choline and cytidine, building blocks used to restore neuronal membrane integrity. Citicoline seems to have different effects on phosphatidylcholine synthesis in younger versus older adults. Phosphatidylcholine is an essential compound for cell membrane integrity and reduces in brain as a result of aging. Clinical data suggest that uridine and choline are the circulating substrates through which citicoline facilitates an increase in brain membrane phospholipid synthesis. Uridine crosses the blood-brain barrier and is converted to uridine triphosphate. Uridine directly gets converted to cytidine triphosphate intracellularly. The frontal lobe is the preferred site for the deposition of Citicoline .

This area of the brain contributes to memory function by supporting attention, memory capacity, and by reducing mental fatigue. Citicoline has benefit in patients experiencing ischemia by decreasing the accumulation of free fatty acids at the site of the lesion, which occurs as a result of neuronal cell damage and death. After the initiation of ischemia, there is a significant increase in arachidonic acid, glycerols, and free fatty acids caused by the breakdown of neuronal membranes.

Toxic metabolites such as prostaglandins, thromboxanes, and free radicals get accumulated, leading to further damage. Intracerebral administration of citicoline prior to induction of ischemia reduces the rise in free fatty acids, arachidonic acid, and other toxic metabolites, attenuating free radical damage and restoring membrane function [23].

Citicoline normalizes neurotransmitter release pattern. In conditions of cerebral hypoxia and ischemia, NE (Nor Epinephrine) release may decrease, while the release of dopamine may increase. Citicoline administration to rats kept in a chronic hypoxic state reduces behavioral deteriorations and increased survival time. It is able to increase the dilation of blood vessels in animals with cerebral microcirculation injury, significantly increasing cerebral blood flow. Citicoline administration to rats increases striatal dopamine synthesis lesions and have shown to regenerate nerve cells. Citicoline enhances the preservation of an inner mitochondrial membrane component known as cardiolipin, which is an important regulatory factor for preservation of mitochondrial function . It also facilitates the preservation of sphingomyelin, which promotes signal transduction in nerve cells and attenuates lipid peroxidation. It has been shown to have direct free-radical suppressive effects. Citicoline treatment significantly increases the length and branch points of dendrites, increasing the overall surface area occupied by neurons, which leads to an increased efficiency of sensory information processing .

Used:- 

Used in the treatment of stroke, head injury, Alzheimer's disease and dementia in Parkinson's disease.

Side Effects:- 

Headache, Edema (swelling), Insomnia (difficulty in sleeping), Anxiety, Hypotension (low blood pressure), Weakness, Gastrointestinal disturbance.

Dose:- 0.5 - 1 g/day i.m. or i.v injection, 200-600mg/day oral in divided doses. As directed by your doctor.