Identification

Name
Choline salicylate
Accession Number
DB14006  (DBSALT001576)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Choline salicylate is an anti-inflammatory pain reliever agent that is related to aspirin. It is used to decrease swelling and to treat mild-moderate pain. It is used to treat arthritis in both children and adults. This medicine can also be used for fever [8].

Choline Salicylate is the choline salt of salicylic acid, used as an analgesic, antipyretic and antirheumatic. It relieves mild to moderate pain and reduce fever and inflammation or swelling. Choline salicylate is effective in the treatment of gout, rheumatic fever, rheumatoid arthritis and muscle injuries [15].

This drug is also a main ingredient in teething gels to relieve pains associated with tooth growth in the infant population [13]. The UK government has regulated its use, due to toxicity in those under 16 years of age. Topical oral salicylate gels are no longer indicated for people younger than 16 years for pain associated with infant teething, orthodontic devices, cold sores, or mouth ulcers [13].

Structure
Thumb
Synonyms
Not Available
Active Moieties
NameKindUNIICASInChI Key
Salicylic acidunknownO414PZ4LPZ69-72-7YGSDEFSMJLZEOE-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DayClear COUGH COLD AND FLUCholine salicylate (870 mg/30mL) + Dextromethorphan hydrobromide monohydrate (20 mg/30mL) + Guaifenesin (200 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL)LiquidOralGm Pharmaceuticals2015-10-20Not applicableUs
DayClear SINUS PAIN AND PRESSURECholine salicylate (870 mg/30mL) + Guaifenesin (200 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL)LiquidOralGm Pharmaceuticals2015-08-10Not applicableUs
First Aid Shot Therapy Hangover ReliefCholine salicylate (870 mg/40mL) + Caffeine (65 mg/40mL)SolutionOralFirst Aid Beverages, Inc.2015-02-01Not applicableUs
First Aid Shot Therapy Pain reliefCholine salicylate (500 mg/40mL) + Caffeine (65 mg/40mL)LiquidOralFirst Aid Beverages, Inc.2013-09-05Not applicableUs
First Aid Shot Therapy Pain ReliefCholine salicylate (650 mg/40mL) + Caffeine (65 mg/40mL)LiquidOralFirst Aid Beverages, Inc.2015-02-01Not applicableUs
Kroger Cough Cold and FluCholine salicylate (870 mg/30mL) + Dextromethorphan hydrobromide monohydrate (20 mg/30mL) + Guaifenesin (200 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL)LiquidOralKroger2016-04-07Not applicableUs
Kroger NiteTime Cold and FluCholine salicylate (870 mg/30mL) + Diphenhydramine hydrochloride (50 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL)LiquidOralKroger2016-04-07Not applicableUs
Kroger Sinus Pain and PressureCholine salicylate (870 mg/30mL) + Guaifenesin (200 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL)LiquidOralKroger2016-04-07Not applicableUs
Niteclear Cold and Flu ReliefCholine salicylate (870 mg/1mL) + Diphenhydramine hydrochloride (50 mg/1mL) + Phenylephrine hydrochloride (10 mg/1mL)SolutionOralGm Pharmaceuticals2015-10-20Not applicableUs
Teejel GelCholine salicylate (8.7 %) + Cetalkonium chloride (0.01 %)GelDental; TopicalPurdue Pharma1965-12-312002-07-30Canada
Categories
UNII
KD510K1IQW
CAS number
2016-36-6
Weight
Average: 241.287
Monoisotopic: 241.131408096
Chemical Formula
C12H19NO4
InChI Key
UDKCHVLMFQVBAA-UHFFFAOYSA-M
InChI
InChI=1S/C7H6O3.C5H14NO/c8-6-4-2-1-3-5(6)7(9)10;1-6(2,3)4-5-7/h1-4,8H,(H,9,10);7H,4-5H2,1-3H3/q;+1/p-1
IUPAC Name
(2-hydroxyethyl)trimethylazanium 2-hydroxybenzoate
SMILES
C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O

Pharmacology

Indication

The oral gel is indicated for the relief of pain and discomfort of common mouth ulcers, cold sores, denture sore spots, infant teething and mouth ulcers, and sore spots due to orthodontic devices in children [14].

Associated Conditions
Pharmacodynamics

This is an anti-inflammatory and antipyretic medication [11], [12].

If is often used in oral gel form for the relief of pain, discomfort, and inflammation caused by common mouth ulcers, cold sores, denture and sore spots, as well as mouth ulcers, and sore spots because of orthodontic devices [18].

Mechanism of action

Choline salicylate relieves pain by inhibition of prostaglandin synthesis and reduces fever by acting on the hypothalamus heat-regulating center. It also inhibits the generation of impulses through the inhibition of cyclooxygenase enzyme (COX) [11], [15].

Cyclooxygenase is involved in the production of prostaglandins, in response to injury and after various other stimuli. The prostaglandins promote pain, swelling, and inflammation. The choline salicylate decreases inflammation and pain by reducing the production of these prostaglandins in the area of the mouth it is applied to [16].

TargetActionsOrganism
UCholine-phosphate cytidylyltransferase B
product of
Human
UAcetylcholinesterase
product of
Human
UCholine-phosphate cytidylyltransferase A
product of
Human
UPhospholipase D2
product of
Human
UCholinesterase
product of
Human
UPhospholipase D1
product of
Human
UPhosphoethanolamine/phosphocholine phosphatase
product of
Human
UNeuronal acetylcholine receptor subunit alpha-7Not AvailableHuman
Absorption

Onset: 1-2 hr after ingestion [12]

In the oral form, choline salicylate is absorbed across the buccal mucosa. There is a need for caution not to exceed the stated dose and monitor for any signs of suggested salicylism, especially when this drug is used for infants [14].

In one study, it was found that this drug was more rapidly absorbed than ASA (absorption t1/2 = 0.1 vs 0.36 h) [17].

Volume of distribution

0.15 L/kg (salicylate), and widely distributed throughout extracellular water and most tissues [18]

Protein binding

Salicylic acid is highly (80-90%) protein bound [18].

Metabolism

The metabolism of salicylic acid is by glycine and phenolic or acyl glucuronate conjugation with small amounts of the drug undergoing hydroxylation [18].

Extensively metabolized in the liver; inactive metabolites are excreted by the kidneys [19].

Route of elimination

Both metabolites of choline salicylate, and a small amount of intact salicylic acid are excreted, primarily in the urine [L1239].

Half life

The plasma half-life of salicylic acid is 2-4 hours [18]. Up to 15 – 30 h with larger doses due to saturation of liver metabolism capacity [19].

Clearance
Not Available
Toxicity

LD50, oral in mouse: 2690mg/kg [4]. Ld50, subcutaneous in mouse: 1gm/kg [4].

Interferes with thyroid function test [11].

Gastrointestinal (GI) disorders, fatigue, hypersensitivity reactions, skin eruptions, hemolytic anemia, weakness, dyspnoea; local irritation (rectally); Reye's syndrome.

Potentially Fatal: Paroxysmal bronchospasm; hepatotoxicity; renal impairment/failure; thrombocytopenia, iron-deficiency anemia, occult bleeding, leukopenia; mild chronic salicylate intoxication [11].

Salicylate poisoning is normally associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths due to salicylate poisoning occur in patients whose serum concentrations of salicylate are over 700 mg/L (5.1 mmol/L). Single doses of less than 100 mg/kg are very unlikely to lead to serious poisoning. Patients should be provided with supportive therapy or treatment for salicylate poisoning as necessary. This may include treatment like activated charcoal, urinary alkalinization and, in severe cases, hemodialysis [18].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
AgmatineThe serum concentration of Agmatine can be increased when it is combined with Choline salicylate.
AlprazolamAlprazolam may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
AmilorideThe serum concentration of Choline salicylate can be increased when it is combined with Amiloride.
AmitriptylineCholine salicylate may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Choline salicylate which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Bochner F, Graham GG, Cham BE, Imhoff DM, Haavisto TM: Salicylate metabolite kinetics after several salicylates. Clin Pharmacol Ther. 1981 Aug;30(2):266-75. [PubMed:7249509]
  2. Needs CJ, Brooks PM: Clinical pharmacokinetics of the salicylates. Clin Pharmacokinet. 1985 Mar-Apr;10(2):164-77. doi: 10.2165/00003088-198510020-00004. [PubMed:3888490]
  3. Kuehl GE, Bigler J, Potter JD, Lampe JW: Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes. Drug Metab Dispos. 2006 Feb;34(2):199-202. doi: 10.1124/dmd.105.005652. Epub 2005 Oct 28. [PubMed:16258079]
  4. Choline Salicylate [Link]
  5. Topical choline salicylates implicated in Reye’s syndrome [Link]
  6. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests. [Link]
  7. Choline Salicylate [Link]
  8. Choline Salicylate; Magnesium Salicylate oral tablet [Link]
  9. Salicylates, Mayo Clinic [Link]
  10. Choline Salicylate drug info, UC Irvine [Link]
  11. Choline Salicylate [Link]
  12. Choline Salicylate [Link]
  13. Oral salicylate gels: not for use in those younger than age 16 years [Link]
  14. Bonjela oral mucosal gel [Link]
  15. Drug Monograph, Choline Salicylate [Link]
  16. Bonjela: treatment for mouth ulcers [Link]
  17. Efficacy, Disposition and Pharmacodynamics of Aspirin, Acetaminophen and Choline Salicylate in Young Febrile Children [Link]
  18. Bonjela [Link]
  19. Choline and magnesium salicylates [Link]
  20. Salicyluric acid [Link]
External Links
KEGG Drug
D00810
ChemSpider
15385
ChEBI
3668
ChEMBL
CHEMBL2104095
Wikipedia
Choline
ATC Codes
N02BA03 — Choline salicylate
MSDS
Download (183 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOral
LiquidOral
GelDental; Topical
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)336.3MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.396 mg/mLALOGPS
logP-0.5ALOGPS
logP1.98ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)2.79ChemAxon
pKa (Strongest Basic)-6.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.36 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity46.13 m3·mol-1ChemAxon
Polarizability12.38 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as salicylic acids. These are ortho-hydroxylated benzoic acids.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Salicylic acids
Alternative Parents
Benzoic acids / Benzoyl derivatives / Cholines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Tetraalkylammonium salts / Carboxylic acid salts / 1,2-aminoalcohols / Carboxylic acids
show 4 more
Substituents
Salicylic acid / Benzoic acid / Benzoyl / 1-hydroxy-4-unsubstituted benzenoid / Choline / Phenol / 1-hydroxy-2-unsubstituted benzenoid / Vinylogous acid / Tetraalkylammonium salt / Quaternary ammonium salt
show 16 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Choline-phosphate cytidylyltransferase activity
Specific Function
Controls phosphatidylcholine synthesis.
Gene Name
PCYT1B
Uniprot ID
Q9Y5K3
Uniprot Name
Choline-phosphate cytidylyltransferase B
Molecular Weight
41939.76 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Wang L, Magdaleno S, Tabas I, Jackowski S: Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol Cell Biol. 2005 Apr;25(8):3357-63. [PubMed:15798219]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Amenta F, Tayebati SK, Vitali D, Di Tullio MA: Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission. Mech Ageing Dev. 2006 Feb;127(2):173-9. Epub 2005 Nov 16. [PubMed:16297435]
  2. Longobardi F, Solfrizzo M, Compagnone D, Del Carlo M, Visconti A: Use of electrochemical biosensor and gas chromatography for determination of dichlorvos in wheat. J Agric Food Chem. 2005 Nov 30;53(24):9389-94. [PubMed:16302752]
  3. Durcan N, Costello RW, McLean WG, Blusztajn J, Madziar B, Fenech AG, Hall IP, Gleich GJ, McGarvey L, Walsh MT: Eosinophil-mediated cholinergic nerve remodeling. Am J Respir Cell Mol Biol. 2006 Jun;34(6):775-86. Epub 2006 Feb 2. [PubMed:16456188]
  4. Alkondon M, Albuquerque EX: Subtype-specific inhibition of nicotinic acetylcholine receptors by choline: a regulatory pathway. J Pharmacol Exp Ther. 2006 Jul;318(1):268-75. Epub 2006 Mar 24. [PubMed:16565162]
  5. Anzai J: [Use of biosensors for detecting organophosphorus agents]. Yakugaku Zasshi. 2006 Dec;126(12):1301-8. [PubMed:17139155]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Lipid binding
Specific Function
Controls phosphatidylcholine synthesis.
Gene Name
PCYT1A
Uniprot ID
P49585
Uniprot Name
Choline-phosphate cytidylyltransferase A
Molecular Weight
41730.67 Da
References
  1. Enaw JO, Zhu H, Yang W, Lu W, Shaw GM, Lammer EJ, Finnell RH: CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population. BMC Med. 2006 Dec 21;4:36. [PubMed:17184542]
  2. Li L, She H, Yue SJ, Qin XQ, Guan CX, Liu HJ, Luo ZQ: Role of c-fos gene in vasoactive intestinal peptide promoted synthesis of pulmonary surfactant phospholipids. Regul Pept. 2007 May 3;140(3):117-24. Epub 2007 Jan 10. [PubMed:17218027]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Phospholipase d activity
Specific Function
May have a role in signal-induced cytoskeletal regulation and/or endocytosis.
Gene Name
PLD2
Uniprot ID
O14939
Uniprot Name
Phospholipase D2
Molecular Weight
105986.1 Da
References
  1. Lee JS, Kim JH, Jang IH, Kim HS, Han JM, Kazlauskas A, Yagisawa H, Suh PG, Ryu SH: Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity. J Cell Sci. 2005 Oct 1;118(Pt 19):4405-13. [PubMed:16179605]
  2. Singh AT, Frohman MA, Stern PH: Parathyroid hormone stimulates phosphatidylethanolamine hydrolysis by phospholipase D in osteoblastic cells. Lipids. 2005 Nov;40(11):1135-40. [PubMed:16459925]
  3. Paruch S, Heinis M, Lemay J, Hoeffel G, Maranon C, Hosmalin A, Perianin A: CCR5 signaling through phospholipase D involves p44/42 MAP-kinases and promotes HIV-1 LTR-directed gene expression. FASEB J. 2007 Dec;21(14):4038-46. Epub 2007 Jul 12. [PubMed:17627030]
  4. Szumilo M, Rahden-Staron I: [Phospholipase D in mammalian cells: structure, properties, physiological and pathological role]. Postepy Hig Med Dosw (Online). 2006;60:421-30. [PubMed:16921342]
  5. Fensome-Green A, Cockcroft S: Reconstitution system based on cytosol-depleted cells to study the regulation of phospholipase D. Methods Mol Biol. 2006;332:299-310. [PubMed:16878701]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Hsieh BC, Matsumoto K, Cheng TJ, Yuu G, Chen RL: Choline biosensor constructed with chitinous membrane from soldier crab and its application in measuring cholinesterase inhibitory activities. J Pharm Biomed Anal. 2007 Nov 30;45(4):673-8. Epub 2007 Jan 24. [PubMed:17329059]
  2. Amenta F, Tayebati SK, Vitali D, Di Tullio MA: Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission. Mech Ageing Dev. 2006 Feb;127(2):173-9. Epub 2005 Nov 16. [PubMed:16297435]
  3. Lurie S, Sadan O, Oron G, Fux A, Boaz M, Ezri T, Golan A, Bar J: Reduced pseudocholinesterase activity in patients with HELLP syndrome. Reprod Sci. 2007 Feb;14(2):192-6. [PubMed:17636231]
  4. Calaf GM, Roy D: Gene expression signature of parathion-transformed human breast epithelial cells. Int J Mol Med. 2007 May;19(5):741-50. [PubMed:17390078]
  5. Stoytcheva M, Zlatev R, Valdez B, Magnin JP, Velkova Z: Electrochemical sensor based on Arthrobacter globiformis for cholinesterase activity determination. Biosens Bioelectron. 2006 Jul 15;22(1):1-9. Epub 2005 Dec 20. [PubMed:16376069]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Phospholipase d activity
Specific Function
Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear int...
Gene Name
PLD1
Uniprot ID
Q13393
Uniprot Name
Phospholipase D1
Molecular Weight
124183.135 Da
References
  1. Lee JS, Kim JH, Jang IH, Kim HS, Han JM, Kazlauskas A, Yagisawa H, Suh PG, Ryu SH: Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity. J Cell Sci. 2005 Oct 1;118(Pt 19):4405-13. [PubMed:16179605]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Product of
General Function
Pyrophosphatase activity
Specific Function
Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho). Involved in the generation of inorganic phosphate for bone mineralization.
Gene Name
PHOSPHO1
Uniprot ID
Q8TCT1
Uniprot Name
Phosphoethanolamine/phosphocholine phosphatase
Molecular Weight
29712.54 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Zhao L, Kuo YP, George AA, Peng JH, Purandare MS, Schroeder KM, Lukas RJ, Wu J: Functional properties of homomeric, human alpha 7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line. J Pharmacol Exp Ther. 2003 Jun;305(3):1132-41. Epub 2003 Mar 6. [PubMed:12626641]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Metal ion binding
Specific Function
Catalyzes both phosphatidylcholine and phosphatidylethanolamine biosynthesis from CDP-choline and CDP-ethanolamine, respectively. Involved in protein-dependent process of phospholipid transport to ...
Gene Name
CEPT1
Uniprot ID
Q9Y6K0
Uniprot Name
Choline/ethanolaminephosphotransferase 1
Molecular Weight
46553.135 Da
References
  1. Wright MM, McMaster CR: PC and PE synthesis: mixed micellar analysis of the cholinephosphotransferase and ethanolaminephosphotransferase activities of human choline/ethanolamine phosphotransferase 1 (CEPT1). Lipids. 2002 Jul;37(7):663-72. [PubMed:12216837]
  2. Henneberry AL, Wistow G, McMaster CR: Cloning, genomic organization, and characterization of a human cholinephosphotransferase. J Biol Chem. 2000 Sep 22;275(38):29808-15. [PubMed:10893425]
  3. Henneberry AL, McMaster CR: Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine. Biochem J. 1999 Apr 15;339 ( Pt 2):291-8. [PubMed:10191259]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Ethanolamine kinase activity
Specific Function
Has a key role in phospholipid biosynthesis. Catalyzes the first step in phosphatidylethanolamine biosynthesis. Phosphorylates ethanolamine, and can also act on choline (in vitro). Has higher activ...
Gene Name
CHKB
Uniprot ID
Q9Y259
Uniprot Name
Choline/ethanolamine kinase
Molecular Weight
45270.99 Da
References
  1. Sher RB, Aoyama C, Huebsch KA, Ji S, Kerner J, Yang Y, Frankel WN, Hoppel CL, Wood PA, Vance DE, Cox GA: A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis. J Biol Chem. 2006 Feb 24;281(8):4938-48. Epub 2005 Dec 21. [PubMed:16371353]
  2. Eliyahu G, Kreizman T, Degani H: Phosphocholine as a biomarker of breast cancer: molecular and biochemical studies. Int J Cancer. 2007 Apr 15;120(8):1721-30. [PubMed:17236204]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Choline o-acetyltransferase activity
Specific Function
Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
Gene Name
CHAT
Uniprot ID
P28329
Uniprot Name
Choline O-acetyltransferase
Molecular Weight
82535.025 Da
References
  1. Kim AR, Dobransky T, Rylett RJ, Shilton BH: Surface-entropy reduction used in the crystallization of human choline acetyltransferase. Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1306-10. Epub 2005 Aug 16. [PubMed:16131766]
  2. Bikopoulos GJ, Hoque T, Webb RA: Infection with the cestode Hymenolepis diminuta induces changes in acetylcholine metabolism and muscarinic receptor mRNA expression in the rat jejunum. Parasitol Res. 2006 Aug;99(3):231-7. Epub 2006 Mar 16. [PubMed:16541262]
  3. Opazo P, Saud K, de Saint Pierre M, Cardenas AM, Allen DD, Segura-Aguilar J, Caviedes R, Caviedes P: Knockdown of amyloid precursor protein normalizes cholinergic function in a cell line derived from the cerebral cortex of a trisomy 16 mouse: An animal model of down syndrome. J Neurosci Res. 2006 Nov 1;84(6):1303-10. [PubMed:16941497]
  4. Kim AR, Rylett RJ, Shilton BH: Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry. 2006 Dec 12;45(49):14621-31. [PubMed:17144655]
  5. Mehl A, Schanke TM, Torvik A, Fonnum F: The effect of trichlorfon and methylazoxymethanol on the development of guinea pig cerebellum. Toxicol Appl Pharmacol. 2007 Mar;219(2-3):128-35. Epub 2006 Nov 1. [PubMed:17150236]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Signal transducer activity
Specific Function
Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthes...
Gene Name
CHKA
Uniprot ID
P35790
Uniprot Name
Choline kinase alpha
Molecular Weight
52248.53 Da
References
  1. Li Z, Agellon LB, Vance DE: Phosphatidylcholine homeostasis and liver failure. J Biol Chem. 2005 Nov 11;280(45):37798-802. Epub 2005 Sep 6. [PubMed:16144842]
  2. Glunde K, Raman V, Mori N, Bhujwalla ZM: RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation. Cancer Res. 2005 Dec 1;65(23):11034-43. [PubMed:16322253]
  3. Malito E, Sekulic N, Too WC, Konrad M, Lavie A: Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J Mol Biol. 2006 Nov 24;364(2):136-51. Epub 2006 Sep 3. [PubMed:17007874]
  4. Eliyahu G, Kreizman T, Degani H: Phosphocholine as a biomarker of breast cancer: molecular and biochemical studies. Int J Cancer. 2007 Apr 15;120(8):1721-30. [PubMed:17236204]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Flavin adenine dinucleotide binding
Specific Function
Not Available
Gene Name
CHDH
Uniprot ID
Q8NE62
Uniprot Name
Choline dehydrogenase, mitochondrial
Molecular Weight
65358.005 Da
References
  1. Slow S, Garrow TA: Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats. J Nutr. 2006 Sep;136(9):2279-83. [PubMed:16920841]
  2. Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G: Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. BMC Cardiovasc Disord. 2007 Jul 13;7:20. [PubMed:17629908]
  3. Quan R, Shang M, Zhang H, Zhao Y, Zhang J: Engineering of enhanced glycine betaine synthesis improves drought tolerance in maize. Plant Biotechnol J. 2004 Nov;2(6):477-86. [PubMed:17147620]
  4. Dalmeijer GW, Olthof MR, Verhoef P, Bots ML, van der Schouw YT: Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr. 2008 Mar;62(3):386-94. Epub 2007 Mar 21. [PubMed:17375117]
  5. da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH: Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006 Jul;20(9):1336-44. [PubMed:16816108]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Sweet DH, Miller DS, Pritchard JB: Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J Biol Chem. 2001 Nov 9;276(45):41611-9. Epub 2001 Sep 11. [PubMed:11553644]
  2. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [PubMed:12089365]
  3. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [PubMed:12176030]
  4. Okuda M, Urakami Y, Saito H, Inui K: Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31. [PubMed:10082798]
  5. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
  6. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [PubMed:9260930]
  7. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [PubMed:11502595]
  8. Budiman T, Bamberg E, Koepsell H, Nagel G: Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat. J Biol Chem. 2000 Sep 22;275(38):29413-20. [PubMed:10889205]
  9. Pan G, Winter TN, Roberts JC, Fairbanks CA, Elmquist WF: Organic cation uptake is enhanced in bcrp1-transfected MDCKII cells. Mol Pharm. 2010 Feb 1;7(1):138-45. doi: 10.1021/mp900177r. [PubMed:19886673]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755]
  2. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [PubMed:9187257]
  3. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [PubMed:9655880]
  4. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [PubMed:12176030]
  5. Zhang L, Dresser MJ, Chun JK, Babbitt PC, Giacomini KM: Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J Biol Chem. 1997 Jun 27;272(26):16548-54. [PubMed:9195965]
  6. Okuda M, Urakami Y, Saito H, Inui K: Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31. [PubMed:10082798]
  7. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
  8. Jonker JW, Wagenaar E, Mol CA, Buitelaar M, Koepsell H, Smit JW, Schinkel AH: Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Mol Cell Biol. 2001 Aug;21(16):5471-7. [PubMed:11463829]
  9. Sinclair CJ, Chi KD, Subramanian V, Ward KL, Green RM: Functional expression of a high affinity mammalian hepatic choline/organic cation transporter. J Lipid Res. 2000 Nov;41(11):1841-8. [PubMed:11060354]
  10. Green RM, Lo K, Sterritt C, Beier DR: Cloning and functional expression of a mouse liver organic cation transporter. Hepatology. 1999 May;29(5):1556-62. [PubMed:10216142]
  11. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. [PubMed:8955087]
  12. Sweet DH, Miller DS, Pritchard JB: Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J Biol Chem. 2001 Nov 9;276(45):41611-9. Epub 2001 Sep 11. [PubMed:11553644]
  13. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
  14. Gorboulev V, Volk C, Arndt P, Akhoundova A, Koepsell H: Selectivity of the polyspecific cation transporter rOCT1 is changed by mutation of aspartate 475 to glutamate. Mol Pharmacol. 1999 Dec;56(6):1254-61. [PubMed:10570053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V: Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem. 1998 Jun 26;273(26):15971-9. [PubMed:9632645]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [PubMed:9618255]
  2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [PubMed:10454528]
  3. Tamai I, Ohashi R, Nezu JI, Sai Y, Kobayashi D, Oku A, Shimane M, Tsuji A: Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem. 2000 Dec 22;275(51):40064-72. [PubMed:11010964]
  4. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [PubMed:11160873]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [PubMed:10215651]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Choline transmembrane transporter activity
Specific Function
Choline transporter. May be involved in membrane synthesis and myelin production.
Gene Name
SLC44A1
Uniprot ID
Q8WWI5
Uniprot Name
Choline transporter-like protein 1
Molecular Weight
73301.28 Da
References
  1. Inazu M, Takeda H, Matsumiya T: Molecular and functional characterization of an Na+-independent choline transporter in rat astrocytes. J Neurochem. 2005 Sep;94(5):1427-37. Epub 2005 Jul 5. [PubMed:16000150]
  2. Fullerton MD, Wagner L, Yuan Z, Bakovic M: Impaired trafficking of choline transporter-like protein-1 at plasma membrane and inhibition of choline transport in THP-1 monocyte-derived macrophages. Am J Physiol Cell Physiol. 2006 Apr;290(4):C1230-8. Epub 2005 Nov 30. [PubMed:16319125]
  3. Tomi M, Arai K, Tachikawa M, Hosoya K: Na(+)-independent choline transport in rat retinal capillary endothelial cells. Neurochem Res. 2007 Nov;32(11):1833-42. Epub 2007 May 23. [PubMed:17520363]
  4. Ishiguro N, Oyabu M, Sato T, Maeda T, Minami H, Tamai I: Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Pharm Res. 2008 Feb;25(2):417-27. Epub 2007 Jul 12. [PubMed:17624579]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
SLC44A4
Uniprot ID
Q53GD3
Uniprot Name
Choline transporter-like protein 4
Molecular Weight
79252.975 Da
References
  1. Tomi M, Arai K, Tachikawa M, Hosoya K: Na(+)-independent choline transport in rat retinal capillary endothelial cells. Neurochem Res. 2007 Nov;32(11):1833-42. Epub 2007 May 23. [PubMed:17520363]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Signal transducer activity
Specific Function
Isoform 1, but not isoform 3, exhibits some choline transporter activity.
Gene Name
SLC44A2
Uniprot ID
Q8IWA5
Uniprot Name
Choline transporter-like protein 2
Molecular Weight
80122.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
SLC44A3
Uniprot ID
Q8N4M1
Uniprot Name
Choline transporter-like protein 3
Molecular Weight
73782.63 Da
References
  1. Tomi M, Arai K, Tachikawa M, Hosoya K: Na(+)-independent choline transport in rat retinal capillary endothelial cells. Neurochem Res. 2007 Nov;32(11):1833-42. Epub 2007 May 23. [PubMed:17520363]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Choline:sodium symporter activity
Specific Function
Imports choline from the extracellular space to the neuron with high affinity. Choline uptake is the rate-limiting step in acetylcholine synthesis. Sodium ion- and chloride ion-dependent.
Gene Name
SLC5A7
Uniprot ID
Q9GZV3
Uniprot Name
High affinity choline transporter 1
Molecular Weight
63202.985 Da
References
  1. Ribeiro FM, Black SA, Cregan SP, Prado VF, Prado MA, Rylett RJ, Ferguson SS: Constitutive high-affinity choline transporter endocytosis is determined by a carboxyl-terminal tail dileucine motif. J Neurochem. 2005 Jul;94(1):86-96. [PubMed:15953352]
  2. Geldenhuys WJ, Lockman PR, Philip AE, McAfee JH, Miller BL, McCurdy CR, Allen DD: Inhibition of choline uptake by N-cyclohexylcholine, a high affinity ligand for the choline transporter at the blood-brain barrier. J Drug Target. 2005 May;13(4):259-66. [PubMed:16051538]
  3. Guidry G, Willison BD, Blakely RD, Landis SC, Habecker BA: Developmental expression of the high affinity choline transporter in cholinergic sympathetic neurons. Auton Neurosci. 2005 Dec 30;123(1-2):54-61. Epub 2005 Nov 8. [PubMed:16278103]
  4. Parikh V, Sarter M: Cortical choline transporter function measured in vivo using choline-sensitive microelectrodes: clearance of endogenous and exogenous choline and effects of removal of cholinergic terminals. J Neurochem. 2006 Apr;97(2):488-503. Epub 2006 Mar 15. [PubMed:16539662]
  5. Parikh V, Apparsundaram S, Kozak R, Richards JB, Sarter M: Reduced expression and capacity of the striatal high-affinity choline transporter in hyperdopaminergic mice. Neuroscience. 2006 Aug 11;141(1):379-89. Epub 2006 May 3. [PubMed:16675138]

Drug created on April 06, 2018 12:09 / Updated on August 02, 2018 07:01