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Pharmaceuticals
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Pharmacology and Medical Uses of Citicoline
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Pharmacology and Medical Uses of Citicoline

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 July 2021)

Special Issue Editor

Dr. Paweł Grieb

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Guest Editor
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
Interests: neuroprotectants; antiglaucoma drugs; anticancer drugs; magnetic resonance techniques

Special Issue Information

Dear Colleagues,

Citicoline is the international non-proprietary name of cytidine-diphosphocholine (CDP-choline), substance playing a pivotal role in the cellular synthesis of phospholipids. In many countries, citicoline-containing drugs are available on prescription since the 1970s. More recently a variant of this substance, citicoline inner salt, has been pronounced a dietary supplement and medicinal food. Over more than fifty years of its medical use, citicoline has proven to be perfectly safe and devoid of any significant side effects. At the same time, there is a continuous influx of new data concerning its effects both on diseased and healthy humans.

Previously, citicoline was popularized as a nootropic and neuroprotective drug and is still best known for its activity supporting various aspects of the central nervous system functions in health and some neurological, sensory, and psychiatric diseases. However, this fascinating molecule may evoke important and potentially beneficial effects in other organs as well, e.g., heart and liver. Authors involved in research on citicoline are invited to submit original and review articles on preclinical as well, as clinical studies, to be published in this Special Issue of Pharmaceuticals.

Dr. Paweł Grieb
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Citicoline
  • Choline
  • Cytidine
  • Neuroprotection
  • Stroke
  • Dementia
  • Glaucoma
  • Memory
  • Cardioprotection
  • Dietary supplement
  • Medicinal food
  • Mood disorders
  • Peripheral neuropathy

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Published Papers (4 papers)

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Research

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12 pages, 1965 KiB  
Communication
Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination
by Viktoria Gudi, Nora Schäfer, Stefan Gingele, Martin Stangel and Thomas Skripuletz
Pharmaceuticals 2021, 14(11), 1156; https://doi.org/10.3390/ph14111156 - 12 Nov 2021
Cited by 5 | Viewed by 4033
Abstract
Inflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails in [...] Read more.
Inflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails in MS. Currently available therapeutics are affecting the immune system, but there is no substance that might enhance remyelination. Cytidine-S-diphosphate choline (CDP-choline), a precursor of the biomembrane component phospholipid phosphatidylcholine was shown to improve remyelination in two animal models of demyelination. However, the doses used in previous animal studies were high (500 mg/kg), and it is not clear if lower doses, which could be applied in human trials, might exert the same beneficial effect on remyelination. The aim of this study was to confirm previous results and to determine the potential regenerative effects of lower doses of CDP-choline (100 and 50 mg/kg). The effects of CDP-choline were investigated in the toxic cuprizone-induced mouse model of de- and remyelination. We found that even low doses of CDP-choline effectively enhanced early remyelination. The beneficial effects on myelin regeneration were accompanied by higher numbers of oligodendrocytes. In conclusion, CDP-choline could become a promising regenerative substance for patients with multiple sclerosis and should be tested in a clinical trial. Full article
(This article belongs to the Special Issue Pharmacology and Medical Uses of Citicoline)
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Review

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22 pages, 1080 KiB  
Review
Role of Citicoline in the Management of Traumatic Brain Injury
by Julio J. Secades
Pharmaceuticals 2021, 14(5), 410; https://doi.org/10.3390/ph14050410 - 26 Apr 2021
Cited by 23 | Viewed by 10281
Abstract
Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is a need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements in the treatment of [...] Read more.
Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is a need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements in the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Moreover, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline is able to accelerate the recovery of consciousness and to improve the outcome of this kind of patient, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI. Full article
(This article belongs to the Special Issue Pharmacology and Medical Uses of Citicoline)
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26 pages, 389 KiB  
Review
Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review
by Francesco Oddone, Luca Rossetti, Mariacristina Parravano, Diego Sbardella, Massimo Coletta, Lucia Ziccardi, Gloria Roberti, Carmela Carnevale, Dario Romano, Gianluca Manni and Vincenzo Parisi
Pharmaceuticals 2021, 14(3), 281; https://doi.org/10.3390/ph14030281 - 20 Mar 2021
Cited by 21 | Viewed by 6377
Abstract
Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial [...] Read more.
Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials). Full article
(This article belongs to the Special Issue Pharmacology and Medical Uses of Citicoline)

Other

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12 pages, 1999 KiB  
Opinion
Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis
by Paweł Grieb, Maciej Świątkiewicz, Agnieszka Kamińska, Anselm Jünemann, Robert Rejdak and Konrad Rejdak
Pharmaceuticals 2021, 14(4), 326; https://doi.org/10.3390/ph14040326 - 2 Apr 2021
Cited by 9 | Viewed by 3772
Abstract
In remitting–relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) [...] Read more.
In remitting–relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) may either retard/attenuate myelin damage or promote/enhance/speed up myelin repair. Almost all currently approved DMTs inhibit myelin damage and are considerably toxic. Enhancement of myelin repair is considered an unmet medical need of MS patients. Citicoline, known for many years as a nootropic and neuroprotective drug and recently pronounced food supplement, has been found to be significantly efficacious in two complementary rodent models of MS, experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced myelin toxicity. Moreover, citicoline treatment improves visual evoked potentials (VEPs) in glaucoma patients, which is relevant because VEP monitoring is frequently used as an indicator of remyelination in MS. Although over-the-counter availability of citicoline may impede its formal translation to the clinic of MS, evaluation of its efficacy for supporting remyelination in this disease is strongly indicated. Full article
(This article belongs to the Special Issue Pharmacology and Medical Uses of Citicoline)
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