Lithium citrate

Identification

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Name
Lithium citrate
Accession Number
DB14507  (DBSALT001430)
Type
Small Molecule
Groups
Approved
Description
Not Available
Structure
Thumb
Synonyms
  • Anhydrous lithium citrate
  • Citric acid, trilithium salt
  • Lithium citrate (anhydrous)
  • Trilithium citrate
Product Ingredients
IngredientUNIICASInChI Key
Lithium citrate tetrahydrate5Z6E9K79YV6080-58-6HXGWMCJZLNWEBC-UHFFFAOYSA-K
Active Moieties
NameKindUNIICASInChI Key
Lithium cationionic8H8Z5UER667439-93-2HBBGRARXTFLTSG-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LithiumSolution8 meq/5mLOralRoxane Laboratories2006-02-172007-04-06Us
LithiumSolution8 meq/5mLOralWest-Ward Pharmaceuticals Corp1980-12-23Not applicableUs
LithiumSolution8 meq/5mLOralPrecision Dose Inc.2012-10-25Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lithium CitrateSyrup8 meq/5mLOralPrecision Dose, Inc.2009-09-292013-09-30Us
PMS-lithium CitrateSyrup8 mmolOralPharmascience Inc1994-12-31Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
3655633623
CAS number
919-16-4
Weight
Average: 209.92
Monoisotopic: 210.05153782
Chemical Formula
C6H5Li3O7
InChI Key
WJSIUCDMWSDDCE-UHFFFAOYSA-K
InChI
InChI=1S/C6H8O7.3Li/c7-3(8)1-6(13,5(11)12)2-4(9)10;;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;;/q;3*+1/p-3
IUPAC Name
trilithium(1+) 2-hydroxypropane-1,2,3-tricarboxylate
SMILES
[Li+].[Li+].[Li+].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O

Pharmacology

Indication

Lithium is used as a mood stabilizer, and is used for treatment of depression and mania. It is often used in bipolar disorder treatment.

Associated Conditions
Pharmacodynamics

Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.

Mechanism of action

The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown. It is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. An increasing number of scientists have come to the conclusion that the excitatory neurotransmitter glutamate is the key factor in understanding how lithium works. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR3), without a shift in reversal potential. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little. It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression. Another mechanism by which lithium might help to regulate mood include the non-competitive inhibition of an enzyme called inositol monophosphatase. Alternately lithium's action may be enhanced through the deactivation of the GSK-3B enzyme. The regulation of GSK-3B by lithium may affect the circadian clock. GSK-3 is known for phosphorylating and thus inactivating glycogen synthase. GSK-3B has also been implicated in the control of cellular response to damaged DNA. GSK-3 normally phosphorylates beta catenin, which leads to beta catenin degratation. When GSK-3 is inhibited, beta catenin increases and transgenic mice with overexpression of beta catenin express similar behaviour to mice treated with lithium. These results suggest that increase of beta catenin may be a possible pathway for the therapeutic action of lithium.

TargetActionsOrganism
UInositol monophosphatase 2Not AvailableHumans
UInositol monophosphatase 1Not AvailableHumans
UGlycogen synthase kinase-3 betaNot AvailableHumans
UGlutamate receptor 3Not AvailableHumans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe serum concentration of Lithium citrate can be increased when it is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of 2,5-Dimethoxy-4-ethylamphetamine can be decreased when used in combination with Lithium citrate.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of 2,5-Dimethoxy-4-ethylthioamphetamine can be decreased when used in combination with Lithium citrate.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of Lithium citrate can be decreased when it is combined with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of 4-Bromo-2,5-dimethoxyamphetamine can be decreased when used in combination with Lithium citrate.
6-O-benzylguanineThe serum concentration of Lithium citrate can be decreased when it is combined with 6-O-benzylguanine.
7-DeazaguanineThe serum concentration of Lithium citrate can be decreased when it is combined with 7-Deazaguanine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Lithium citrate.
7,9-DimethylguanineThe serum concentration of Lithium citrate can be decreased when it is combined with 7,9-Dimethylguanine.
8-azaguanineThe serum concentration of Lithium citrate can be decreased when it is combined with 8-azaguanine.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK: Novel insights into lithium's mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62(1):50-60. doi: 10.1159/000314310. Epub 2010 May 7. [PubMed:20453535]
  2. ILO: Lithium [Link]
External Links
ChemSpider
12932
ChEBI
64735
ChEMBL
CHEMBL1201170
Wikipedia
Lithium_citrate
AHFS Codes
  • 28:28.00 — Antimanic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentNeoplasms, Colorectal / Neoplasms, Esophageal / Stomach Neoplasms1
2CompletedTreatmentDepression1
Not AvailableCompletedBasic ScienceHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOral8 meq/5mL
SyrupOral8 meq/5mL
SyrupOral8 mmol
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility194.0 mg/mLALOGPS
logP-0.54ALOGPS
logP-1.3ChemAxon
logS-0.04ALOGPS
pKa (Strongest Acidic)3.05ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area140.62 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity68.14 m3·mol-1ChemAxon
Polarizability14.23 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lith...
Gene Name
IMPA2
Uniprot ID
O14732
Uniprot Name
Inositol monophosphatase 2
Molecular Weight
31320.525 Da
References
  1. Cryns K, Shamir A, Shapiro J, Daneels G, Goris I, Van Craenendonck H, Straetemans R, Belmaker RH, Agam G, Moechars D, Steckler T: Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice. Neuropsychopharmacology. 2007 Apr;32(4):881-91. Epub 2006 Jul 12. [PubMed:16841073]
  2. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T: Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. [PubMed:17068342]
  3. Ohnishi T, Yamada K, Ohba H, Iwayama Y, Toyota T, Hattori E, Inada T, Kunugi H, Tatsumi M, Ozaki N, Iwata N, Sakamoto K, Iijima Y, Iwata Y, Tsuchiya KJ, Sugihara G, Nanko S, Osumi N, Detera-Wadleigh SD, Kato T, Yoshikawa T: A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription. Neuropsychopharmacology. 2007 Aug;32(8):1727-37. Epub 2007 Jan 24. [PubMed:17251911]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain....
Gene Name
IMPA1
Uniprot ID
P29218
Uniprot Name
Inositol monophosphatase 1
Molecular Weight
30188.59 Da
References
  1. Sarkar S, Rubinsztein DC: Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy. 2006 Apr-Jun;2(2):132-4. Epub 2006 Apr 6. [PubMed:16874097]
  2. Trinquet E, Fink M, Bazin H, Grillet F, Maurin F, Bourrier E, Ansanay H, Leroy C, Michaud A, Durroux T, Maurel D, Malhaire F, Goudet C, Pin JP, Naval M, Hernout O, Chretien F, Chapleur Y, Mathis G: D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate to monitor G protein-coupled receptor activation. Anal Biochem. 2006 Nov 1;358(1):126-35. Epub 2006 Aug 30. [PubMed:16965760]
  3. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T: Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. [PubMed:17068342]
  4. Tanizawa Y, Kuhara A, Inada H, Kodama E, Mizuno T, Mori I: Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans. Genes Dev. 2006 Dec 1;20(23):3296-310. [PubMed:17158747]
  5. Ohnishi T, Yamada K, Ohba H, Iwayama Y, Toyota T, Hattori E, Inada T, Kunugi H, Tatsumi M, Ozaki N, Iwata N, Sakamoto K, Iijima Y, Iwata Y, Tsuchiya KJ, Sugihara G, Nanko S, Osumi N, Detera-Wadleigh SD, Kato T, Yoshikawa T: A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription. Neuropsychopharmacology. 2007 Aug;32(8):1727-37. Epub 2007 Jan 24. [PubMed:17251911]
  6. Li Z, Stieglitz KA, Shrout AL, Wei Y, Weis RM, Stec B, Roberts MF: Mobile loop mutations in an archaeal inositol monophosphatase: modulating three-metal ion assisted catalysis and lithium inhibition. Protein Sci. 2010 Feb;19(2):309-18. doi: 10.1002/pro.315. [PubMed:20027624]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by pho...
Gene Name
GSK3B
Uniprot ID
P49841
Uniprot Name
Glycogen synthase kinase-3 beta
Molecular Weight
46743.865 Da
References
  1. Borsotto M, Cavarec L, Bouillot M, Romey G, Macciardi F, Delaye A, Nasroune M, Bastucci M, Sambucy JL, Luan JJ, Charpagne A, Jouet V, Leger R, Lazdunski M, Cohen D, Chumakov I: PP2A-Bgamma subunit and KCNQ2 K+ channels in bipolar disorder. Pharmacogenomics J. 2007 Apr;7(2):123-32. Epub 2006 May 30. [PubMed:16733521]
  2. Adli M, Hollinde DL, Stamm T, Wiethoff K, Tsahuridu M, Kirchheiner J, Heinz A, Bauer M: Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta -50T/C single nucleotide polymorphism. Biol Psychiatry. 2007 Dec 1;62(11):1295-302. Epub 2007 Jul 12. [PubMed:17628506]
  3. O'Brien WT, Klein PS: Validating GSK3 as an in vivo target of lithium action. Biochem Soc Trans. 2009 Oct;37(Pt 5):1133-8. doi: 10.1042/BST0371133. [PubMed:19754466]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Extracellular-glutamate-gated ion channel activity
Specific Function
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory ne...
Gene Name
GRIA3
Uniprot ID
P42263
Uniprot Name
Glutamate receptor 3
Molecular Weight
101155.975 Da
References
  1. Karkanias NB, Papke RL: Lithium modulates desensitization of the glutamate receptor subtype gluR3 in Xenopus oocytes. Neurosci Lett. 1999 Dec 31;277(3):153-6. [PubMed:10626836]

Drug created on July 11, 2018 15:57 / Updated on June 14, 2019 18:11