Miracoline

Capsule: Each capsule contains: Citicoline (as Sodium), USP 500 mg.
Citicoline is a derivative of choline and cytidine that is involved in the biosynthesis of lecithin. It is claimed to increase blood flow and oxygen consumption in the brain and has been given in the treatment of cerebrovascular disorders, Parkinsonism, and head injury. Citicoline is an interneuronal communication enhancer. It increases the neurotransmission levels because it favors the synthesis and production speed of dopamine in the striatum, acting then as a dopaminergic agonist thru the inhibition of tyrosine-hydroxylase.
Citicoline acts as a presynaptic cholinergic agent which favors the synthesis of acetylcholine. It also decreases the release of serotonin.
Citicoline makes the neurons more active, causing the astrocytes to loosen their grip on the capillaries, thus improving microcirculation. By virtue of this action, Citicoline has an indirect effect on microcirculation. It has the ability to slightly increase cerebral blood flow and exerts an anti-aggregation effect on platelets.
Film-coated tablet: Each film-coated tablet contains: Citicoline (as sodium) 1 g.

Pharmacology: PHARMACODYNAMICS: Capsule: 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 can 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.
Film-coated tablet: Citicoline is a complex organic molecule that functions as an intermediate in the biosynthesis of cell membrane phospholipids. Citicoline is also known as CDP-choline or cytidine diphosphate choline (cytidine 5'-diphosphocholine). CDP-choline belongs to the group of biomolecules in living systems known as nucleotides that play important roles in cellular metabolism. The pharmacologic action of citicoline appears to involve mechanisms that extend beyond phospholipid metabolism. Citicoline metabolites, i.e. choline, methionine, betaine, and cytidine-derived nucleotides - enter a number of metabolic pathways. Biochemical markers of cholinergic nerve transmission are known to be deficient in conditions characterized by degeneration of cholinergic neurons, such as Alzheimer's disease. Citicoline modestly improves cognitive function in Alzheimer's disease by serving as an acetylcholine precursor. The brain uses choline preferentially for acetylcholine synthesis which can limit the amount of choline available for phosphatidylcholine production. Citicoline has been investigated as a therapy for stroke patients. Three mechanisms are postulated: {1) repair of the neuronal membrane via increased synthesis of phosphatidylcholine: (2) repair of damaged cholinergic neurons via potentiation of acetylcholine production. and (3) reduction of free fatty acid build-up at the site of stroke-induced nerve damage. Citicoline protects cholinergic neurons from autocannibalism, a process in which membrane phospholipids are catabolized to provide choline for the synthesis of acetylcholine. This occurs when choline supplies are depleted, necessitating sacrifice of membrane phospholipids to maintain neurotransmission As an exogenous source of choline for acetylcholine production, citicoline thus spares membrane phospholipids (in particular, phosphatidylcholine) and prevents neuronal cell death.
PHARMACOKINETICS: Capsule: Citicoline is a water-soluble, with more than 90% oral bioavailability. Pharmacokinetic studies in healthy adults have shown oral doses of citicoline to be rapidly absorbed, with less than 1 % excreted in the feces. Plasma levels peak in a biphasic manner, at 1 hour after ingestion followed by a second larger peak at 24 hours post-dosing.
Citicoline is metabolized in the gut wall and liver. The byproducts of exogenous citicoline formed by hydrolysis in the intestinal wall are choline and cytidine. After adsorption, choline and cytidine are dispersed throughout the body, enter systemic circulation for utilization in various biosynthetic pathways and cross the blood-brain barrier for re-synthesis into citicoline in the brain.
Pharmacokinetic studies using 14C citicoline show citicoline elimination occurs mainly via respiratory CO₂ and urinary excretion, in two phases, mirroring the biphasic plasma peaks. The initial peak in plasma concentration is followed by a sharp decline, which then slows over the next 4 to 10 hours. In the second phase, an initially rapid decline after the 24-flour plasma peak similarly followed by a slower elimination rate. The elimination half-life is 56 hours for CO₂ and 71 hours for urinary excretion.
Film-coated tablet: Citicoline is a water-soluble compound with greater than 90% bioavailability. Pharmacokinetic studies in healthy adults have shown oral doses of Citicoline to be rapidly absorbed, with less than one percent excreted in the feces. Plasma levels peak in a biphasic manner, at one hour after ingestion followed by a second larger peak at 24 hours post-dosing. Citicoline is metabolized in the gut wall and liver. The byproducts of exogenous Citicoline formed by hydrolysis in the intestinal wall are choline and cytidine. After absorption, choline and cytidine are dispersed throughout the body, enter systemic circulation for utilization in various biosynthetic pathways and cross the blood-brain barrier for re-synthesis into Citicoline in the brain. Pharmacokinetic studies using ¹⁴C Citicoline show Citicoline elimination occurs mainly via respiratory CO₂ and urinary excretion, in two phases, mirroring the biphasic plasma peaks. The initial peak in plasma concentration is followed by a sharp decline, which then slows over the next 4 to 10 hours In the second phase, an initially rapid decline after the 24-hour plasma peak is similarly followed by a slower elimination rate. The elimination half-life is 56 hours for CO₂ and 71 hours for urinary excretion.

Capsule: To increase blood flow and oxygen consumption in the brain and has been given in the treatment of cerebrovascular disorders (including ischaemic stroke), parkinsonism, and head injury.
Film-coated tablet: Used in the treatment of cerebrovascular disorders (including ischaemic stroke), Parkinsonism and head injury.

Capsule: 500 mg capsule - once or twice a day or as prescribed by the physician.
Film-coated tablet: The usual dose is one tablet (1 g) once daily or as prescribed by the physician.

OVERDOSE AND TREATMENT: Capsule: Citicoline exhibits very low toxicity profile in humans. In clinical use it has been observed to be safe at doses up to 2g/day.
The LD₅₀ of a single IV dose of citicoline was 4.6 and 4.15 g/kg in mice and rats, respectively. An oral LD₅₀ could not be determined as no deaths occurred at the maximum possible oral dose. In an unpublished acute toxicity study, free-base citicoline was administered to male and female rats at a dose of 2 g/kg body weight for 14 days. No changes in body weight, deaths, clinical symptoms, or gross pathological changes were observed.
Film-coated tablet: Citicoline exhibits very low toxicity profile in humans. In clinical use it has been observed to be safe at doses up lo 2g/day.

Capsule: Must not be administered to patients with hypertonia of the parasympathetic.
Film-coated tablet: Hypersensitivity to any component of the product. Patients with hypertonia of the parasympathetic nervous system.

Capsule: Large doses of citicoline could aggravate increase in cerebral blood flow in episodes of persistent intracranial hemorrhage.

Capsule: Citicoline should be used with caution in patients with acute, severe, and progressive disturbances, intracranial pressure relieving drugs or use measures to keep body temperature low. Film-coated tablet: Large doses of citicoline could aggravate increase in cerebral blood flow in episodes of persistent intracranial hemorrhage.
Use in Children: Film-coated tablet: No data on use in children.

Capsule: There is inadequate evidence of safe use of Citicoline in human pregnancy. It should be used in pregnancy and lactation only, if the potential benefits justify the potential risks. Caution should be exercised during breastfeeding. because it is not known whether citicoline is excreted in human breast milk.
Film-coated tablet: There is not enough evidence on citicoline's safety in pregnant and breastfeeding women. Citicoline should be used in pregnancy and breastfeeding only when benefits justify the potential risks.

Capsule: Increased parasympathetic effects, fleeting and discrete hypotensor effect.
Film-coated tablet: Cardiovascular: Bradycardia, tachycardia, hypotension.
Gastrointestinal: Diarrhea, epigastric distress, stomach pain.
Nervous: Dizziness, headache, fatigue.
Skin: Rash.

Citicoline potentiates the effects of L-dopa. It must not be administered with meclofenoxate.

Store at temperatures not exceeding 30°C.

Nootropics & Neurotonics/Neurotrophics

N06BX06 - citicoline ; Belongs to the class of other psychostimulants and nootropics.

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