Background and overview[1][2]
In the 1950s, Kennedy et al. discovered citicoline, then chemically synthesized it and determined its molecular structure. Rossiter further discovered in 1957 that citicoline is closely related to phospholipid metabolism and is an important coenzyme in the biosynthesis of phosphatidylcholine (lecithin). The research and development of neuroprotective drugs began in 1963, when Nicholin (Citicol-ine) was first developed by Takeda Corporation of Japan and successfully used to treat disorders of consciousness. After that, a lot of research work was carried out on citicoline at home and abroad, especially in the 1990s, with in-depth discussions in animal models and clinical trials.
Citicoline is an endogenous nucleoside naturally produced in the body and is an intermediate in the main pathway of cell membrane phospholipid biosynthesis. Repair of nerve cell membranes requires large amounts of Citicoline. Supplementing exogenous citicoline can promote the synthesis of nerve cell membrane phospholipids. Citicoline plays an extremely important role in maintaining a variety of cellular physiological processes. Citicoline has obvious clinical therapeutic effect in a variety of cell membrane dysfunction and degenerative diseases caused by ischemia and hemorrhage.
Function[1]
Exogenous cytosine epoxidized soybean oil price phosphocholine can be hydrolyzed to decompose cytidine and choline. The decomposed choline and cytidine can be re-phosphorylated, and catalyzed by cytidine triphosphate-phosphocholine cytidine transferase, cytidine triphosphate and choline monophosphate synthesize citicoline. Citicoline and diacylglycerol synthesize phosphatidylcholine, which forms the bilayer lipid structure of the cell membrane.
The choline decomposed from citicoline is acetylated to produce the neurotransmitter acetylcholine. Betaine, another product decomposed from choline, generates S-adenosyl-L-methionine through the methionine pathway, and finally further synthesizes glutathione with antioxidant effects. In vitro experiments have confirmed that choline deficiency degrades phosphatidylcholine and sphingomyelin in nerve cell membranes, thereby causing cell apoptosis. Due to the continuous replenishment of choline in the catabolism of exogenous citicoline, nerve cell membrane damage and cholinergic nerve death can be prevented.
Citicoline is a normal component of the human body. The molecule contains choline and cytosine. It promotes the synthesis of lecithin in the body and changes the physiological functions of the meninges. Currently, citicoline preparations are mainly used clinically. It is a routine clinical drug used in neurology to improve brain metabolism and has the following characteristics:
1. Reduce cerebral vascular resistance, increase cerebral blood flow, promote brain substance metabolism, and improve cerebral circulation;
2. Enhance the function of the brainstem reticular structure, enhance the function of the pyramidal system, improve motor paralysis, promote lecithin synthesis, and improve the metabolism of imported polymer flocculant in the brain. It can be combined with brain polypeptides to synergistically improve brain function. Function;
3. The main indications are acute craniocerebral trauma and disturbance of consciousness after brain surgery;
4. It is also clinically used for other functional and consciousness disorders caused by acute damage to the central nervous system, paralysis tremens, tinnitus and neurological deafness, sleeping pill poisoning, etc.;
5. In recent years, it has been widely used clinically for ischemic stroke, cerebral arteriosclerosis, multi-infarct dementia, Alzheimer’s disease, viral encephalitis in children, etc.
Citicoline sodium is mainly used clinically to treat neurological sequelae caused by craniocerebral injuries and cerebrovascular accidents. It can also be used to treat Parkinson’s syndrome and has a certain effect on Alzheimer’s disease. ; Used to treat cerebrovascular and cardiovascular diseases; others, such as delaying aging, improving learning effects and memory, etc., also have certain effects. However, injections and freeze-dried powder injections have been mainly used in clinical practice, which is very inconvenient for the later recovery and treatment of brain diseases. For patients who need to use this drug for a long time, the development of easy-to-use oral preparations is of very practical significance; according to clinical use reports, the main adverse reactions of citicoline sodium are gastrointestinal reactions, nausea, stomach pain, and stomach burning. Feeling etc.
Apply[3]
1. Citicoline can restore the structure of cell membranes after brain cell damage, enhance the function of cell membranes, and improve the function of neurons; 2. It can reduce cerebral vascular resistance, increase cerebral blood flow, promote brain metabolism, and improve cerebral circulation. , improve brain function; 3. IncreaseIncreases the secretion of neurotransmitters including acetylcholine and dopamine, enhances the function of the brainstem reticular structure related to consciousness, improves the body’s state of consciousness, and increases the speed of awakening; 4. It can also inhibit the activation of phospholipase A2, thereby accelerating Reabsorption of cerebral edema. 5. It can enhance dopaminergic activity and regulate extrapyramidal physiological functions. 6. It has been proven to have the function of increasing memory and promoting learning.
Citicoline has been classified as a neuroprotective agent, but its direct treatment of acute ischemic stroke has not yet reached a firm conclusion. The international community has proposed a combination treatment plan with citicoline. Different therapeutic drugs will be explored to prevent the cascade reaction of stroke, that is, the pathophysiological and biochemical reactions triggered by cerebral ischemia. For example, combined treatment after focal cerebral ischemia The application of low-dose citicoline and diazepine or basic fibroblast growth factor can significantly reduce the infarct volume, but the use of a low-dose drug alone is ineffective. Combination therapy also includes the combination of thrombolytics and neuroprotective agents. It is hoped that more effective neuroprotective treatments for acute ischemic stroke will soon become available, and that such treatments can be combined with thrombolysis to enhance the therapeutic effect.
Main reference materials
[1] Yu Fangfang, Ouyang Cun, Shen Liya, & Zhang Xiaoqin. (2004). Clinical evaluation of citicoline in the treatment of cerebral hemorrhage. Journal of Pharmacoepidemiology, 13(4), 178-180.
[2] Ye Lin, Fan Hangui, & Li Daoquan. (2005). The efficacy of citicoline combined with physical therapy in the treatment of amblyopia in the elderly. Medical Herald, 24(7), 595-597.
[3] Zhou Changkui, & Wu Xiaohua. (2004). Research progress on neuroprotective agent-citicoline. Chinese Journal of Biochemical Drugs, 25(4), 255-256.
