CITICOLINE

Possibly Marketed Outside US

First approved in 2023

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H25N4O11P2.H
Molecular Weight	488.324
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H+].C[N+](C)(C)CCOP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=CC(N)=NC2=O

InChI

InChIKey=RZZPDXZPRHQOCG-OJAKKHQRSA-N

InChI=1S/C14H26N4O11P2/c1-18(2,3)6-7-26-30(22,23)29-31(24,25)27-8-9-11(19)12(20)13(28-9)17-5-4-10(15)16-14(17)21/h4-5,9,11-13,19-20H,6-8H2,1-3H3,(H3-,15,16,21,22,23,24,25)/t9-,11-,12-,13-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C14H26N4O11P2
Molecular Weight	488.324
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry
Defined Stereocenters	4 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27234918 | https://www.ncbi.nlm.nih.gov/pubmed/17873684 | https://www.ncbi.nlm.nih.gov/pubmed/15005642

Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is a novel nutrient with a broad spectrum of benefits for conditions associated with symptoms of neurological dysfunction shows promise of clinical efficacy in elderly patients with cognitive deficits, inefficient memory, and early-stage Alzheimer's disease. Citicoline has also been investigated as a therapy in stroke patient. Despite it was approved in some countries for treatment Traumatic Brain Injury (TBI), the use of this drug for acute TBI seems to have no field of support anymore, whereas it may have some benefits in improving the neuro-cognitive state in chronic TBI patients. It's also recommended to keep in mind acute interventions like Psychological First Aid (PFA) during acute TBI management. Citicoline plays several important roles in human physiology, including enhancement of structural integrity and signaling for cell membranes, support of acetylcholine synthesis, and synthesis of betaine, a methyl donor. The precise mechanism of action of Citicoline to treat disease is unknown, but was confirmed, that drug might increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. In addition, was shown, that citicoline modulates phospholipids metabolism and neurotransmitter levels and appears to improve cognition in some central nervous system disorders such as bipolar disorder and cocaine dependence. Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric disorder. Cocaine use is particularly common in patients with bipolar disorder.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
phosphatidylcholine 2 Target ID: phosphatidylcholine Sources: https://www.ncbi.nlm.nih.gov/pubmed/12021827	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Traumatic brain injury 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28039682	Primary	Approved 8583	Unknown Approved Use Unknown
Acute ischemic stroke 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27234918	Primary	Approved 8583	Unknown Approved Use Unknown
Alcohol addiction 24 Sources: https://clinicaltrials.gov/ct2/show/NCT02074735	Palliative	Phase IV 63	Unknown Approved Use Unknown
Bipolar disorder 34 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17873684	Palliative	Phase IV 63	Unknown Approved Use Unknown
Cocaine addiction 29 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17873684	Palliative	Phase IV 63	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.085 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.011 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
127.778 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
145.912 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
66.348 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
74.119 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22951317/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		CITICOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1000 mg 2 times / day multiple, oral Recommended Dose: 1000 mg, 2 times / day Route: oral Route: multiple Dose: 1000 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11706098/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11706098/	Sources: https://pubmed.ncbi.nlm.nih.gov/11706098/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 OATP1B1 1079

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMzE3MDAifX0=	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMzE3MDAifX0=	yes [Inhibition 10 uM]

PubMed

Title	Date	PubMed
Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke.	2013-09	23600725
Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study.	2010-04	20043005
Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification.	2008-04-01	18164358
A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence.	2007-10	17873684
Effects of citicoline on experimental spinal cord injury.	2005-11	16257217
Effects of simvastatin on the expression of intercellular adhesion molecule-1 mRNA in neonatal brain with hypoxic-ischemic damage.	2005-08	16193989
The late negative episodic memory effect: the effect of recapitulating study details at test.	2005-05	15820627
Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders.	2005-01	15756928
Elevated erythrocyte CDP-choline levels associated with beta-thalassaemia in patients with transfusion independent anaemia.	2004-10	15571243
Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells.	2002-12-06	12443983
Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study.	2002-05	12021827
Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects.	2001-09	11594440
[Usefulness of SPECT images in helping radiologists understand brain diseases].	2001-04	11398344
Pharmacotherapies for cocaine dependence.	2000-12	11123003
Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion.	1999-11	10669911
Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report.	1999-02	10102764
Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects.	1998-02	9523091
A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group.	1997-09	9305321
A family with chronic haemolysis and selective accumulation of erythrocyte CDP-choline.	1997-08	9264395
Citicoline improves memory performance in elderly subjects.	1997-04	9203170
Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline.	1995	7869846
Efficacy of CDP-choline in the treatment of senile alterations in memory.	1991	1776744
Effects of citicholine and of the combination citicholine + piracetam on the memory (experiments on mice).	1990	2392950
Memory effects of the new derivative of the p-chlorophenoxyacetic acid adafenoxate compared to the effects of some cognition-enhancing drugs in rats.	1989-09	2511850
Selective accumulation of cytosol CDP-choline as an isolated erythrocyte defect in chronic hemolysis.	1983-05	6574471

Patents

Sample Use Guides

In Vivo Use Guide

1000 mg twice a day orally or enterally. The first dose is within 24 hours of injury and treatment continues for 90-days or until the 90-day outcome assessment.

Route of Administration: Oral

In Vitro Use Guide

Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells (EC) through pathways involving ERK1/2 and insulin receptor substrate-1. hCMEC/D3 cells were seeded at a concentration of 8 × 104 cells/ml in 500 μl of complete basal medium in each well of 24-well plate. After 4 h, the medium was changed to serum-poor medium (SPM) containing 1% FBS containing different concentrations of citicoline (1 μM, 10 μM and 100 μM; NOTE; pilot experiments were carried out using 1-100 μM citicoline and optimized for the use of 10 μM subsequently as this produced the most prominent responses). It was discovered that insulin receptor substrate-1 (IRS-1) represented a potent modulator of pro-angiogenic signalling cascades in vascular EC, thus was shown that citicoline induces phosphorylation of IRS-1 and concomitant EC activation and increased vascularisation, that could be a key novel mechanism of action of citicoline.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:50:46 GMT 2025` Edited by `admin` on `Wed Apr 02 08:50:46 GMT 2025`
Record UNII	536BQ2JVC7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NICHOLIN

Preferred Name

English

CITICOLINE

Official Name

English

CITICOLINE [USP-RS]

Common Name

English

IP 302

Code

English

CITICOLINE [JAN]

Common Name

English

CITICOLINE [VANDF]

Common Name

English

CDP-CHOLINE

Common Name

English

citicoline [INN]

Common Name

English

CYTIDINE 5'-(TRIHYDROGEN DIPHOSPHATE), P'-(2-(TRIMETHYLAMMONIO)ETHYL) ESTER, INNER SALT

Common Name

English

CITICOLINE [MART.]

Common Name

English

NSC-122002

Code

English

CYTIDINE 5'-DIPHOSPHATE CHOLINE

Common Name

English

Citicoline [WHO-DD]

Common Name

English

IP-302

Code

English

CITICOLINE [MI]

Common Name

English

Classification Tree Code System Code

DSLD

410 (Number of products:116)