Citicoline

Citicoline stimulates the biosynthesis of structural phospholipids of the neuronal membrane as it is demonstrated in the magnetic resonance spectroscopy studies. Citicoline, through this action, improves the function of the membrane mechanisms, such as the functioning of the ionic exchange pumps and receptors inserted in the latter, the modulation of which is indispensable in the neurotransmission.

Citicoline due to its membrane stabilising activity has properties which favour brain oedema reabsorption.

Experimental studies showed that citicoline inhibits the activation of some phospholipases (A1, A2, C and D), reducing the formation of free radicals, avoiding the destruction of membranous systems and preserving antioxidant defence systems as glutation.

Citicoline preserves the neuronal energetic reserve, inhibits apoptosis and stimulates acetylcholine synthesis

It has been experimentally shown that citicoline also exerts a prophylactic neuroprotective effect in focal brain ischemic models.

Clinical trials showed that citicoline significantly increases the functional evolution of patients with acute ischemic cerebrovascular accident, coinciding with a lower growth of the brain ischemic injury in neuroimaging tests.

In patients with craniocerebral traumatisms, citicoline speeds up their recuperation and reduces the duration and intensity of the post-concussional syndrome.

Citicoline improves the level of attention and consciousness and acts favourably over amnesia and cognitive and neurological disorders associated to brain ischemia.

Citicoline is well absorbed after oral, intramuscular or intravenous administration. Plasma choline levels significantly increase through the aforementioned routes. Oral absorption is nearly complete and its bioavailability is approximately the same as the intravenous route. The medicine is metabolized in the intestine wall and in the liver to choline and cytidine. The administered citicoline is widely distributed in brain structures, with a quick incorporation of the choline fraction in structural phospholipids and the cytidine fraction in cytidinic nucleotides and nucleic acids. Citicoline reaches the brain and it is actively incorporated to cellular, cytoplasmatic and mitochondrial membranes, taking part of the structural phospholipids fraction.

Only a small amount of the dose appears in urine and faeces (less than 3%). Approximately 12% of the dose is eliminated via expired CO₂. In the urinary excretion of the drug, two phases can be distinguished: a first phase, around 36 hours, where the excretion speed rapidly decreases, and a second phase where excretion speed decreases much slower. The same happens with expired CO₂, the elimination speed rapidly decreases after approximately 15 hours and later it decreases much slower.

Oral (1.5 g/kg/day during 6 months in dogs) and intraperitoneal (1g/kg/day during 12 weeks in rats) chronic toxicity studies did not show significant abnormalities related with the administration of the drug. Intravenous administration of 300-500 mg/kg/day of citicoline during 3 months in dogs only produced toxic signs immediately after the injection, such as occasional vomiting, diarrhoea and hyper-salivation.

800 mg/kg of citicoline was administered to albino rabbits during the organogenesis phase, that is, from 7^th to 18^th gestation day. The animals were sacrificed on the 29^th day and a detailed exam of foetus and their mothers was carried out. No maternal or embryo-foetal toxicity signs were observed. The effects over organogenesis were inappreciable, only 10% of the treated foetus showed a slight delay in brain osteogenesis.