Identification
- Generic Name
- Lithium citrate
- DrugBank Accession Number
- DB14507
- Background
Not Available
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lithium citrate (DB14507)
- Weight
- Average: 209.92
Monoisotopic: 210.05153782 - Chemical Formula
- C6H5Li3O7
- Synonyms
- Anhydrous lithium citrate
- Citric acid, trilithium salt
- Lithium citrate (anhydrous)
- Trilithium citrate
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.
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- Contraindications & Blackbox Warnings
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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.
Target Actions Organism UInositol monophosphatase 2 Not Available Humans UInositol monophosphatase 1 Not Available Humans UGlycogen synthase kinase-3 beta Not Available Humans UGlutamate receptor 3 Not Available Humans - 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
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Lithium citrate may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Lithium citrate which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Lithium citrate which could result in a higher serum level. Acenocoumarol The risk or severity of adverse effects can be increased when Lithium citrate is combined with Acenocoumarol. Acetaminophen Lithium citrate may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetazolamide The absorption of Lithium citrate can be decreased when combined with Acetazolamide. Acetophenazine Lithium citrate may increase the neurotoxic activities of Acetophenazine. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Lithium citrate which could result in a higher serum level. Aclidinium Lithium citrate may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Lithium citrate may decrease the excretion rate of Acrivastine which could result in a higher serum level. 
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- Avoid alcohol.
- Avoid iodine-containing foods and supplements.
- Drink plenty of fluids. Drink at least 2500 to 3000 mL of fluids daily.
- Limit caffeine intake.
- Take with food. Lithium can cause hyponatremia. Include adequate salt in the diet.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Lithium citrate tetrahydrate 5Z6E9K79YV 6080-58-6 HXGWMCJZLNWEBC-UHFFFAOYSA-K - Active Moieties
Name Kind UNII CAS InChI Key Lithium cation ionic 8H8Z5UER66 7439-93-2 HBBGRARXTFLTSG-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lithium Solution 8 meq/5mL Oral Roxane Laboratories 2006-02-17 2007-04-06 US 
Lithium Solution 8 meq/5mL Oral Hikma Pharmaceuticals USA Inc. 1980-12-23 2022-08-31 US Lithium Solution 8 meq/5mL Oral Precision Dose Inc. 2012-10-25 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lithium Solution 8 meq/5mL Oral Advagen Pharma Ltd 2022-11-09 Not applicable US Lithium Citrate Syrup 8 meq/5mL Oral Precision Dose, Inc. 2009-09-29 2013-09-30 US PMS-lithium Citrate Syrup 8 mmol / 5 mL Oral Pharmascience Inc 1994-12-31 Not applicable Canada 
Categories
- Drug Categories
- Acids, Acyclic
- Antidepressive Agents
- Antimanic Agents
- Central Nervous System Depressants
- Lithium Compounds
- Mood Stabilizer
- Narrow Therapeutic Index Drugs
- Nephrotoxic agents
- Neurotoxic agents
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Tricarboxylic Acids
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tricarboxylic acids and derivatives. These are carboxylic acids containing exactly three carboxyl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Tricarboxylic acids and derivatives
- Direct Parent
- Tricarboxylic acids and derivatives
- Alternative Parents
- Tertiary alcohols / Carboxylic acid salts / Organic lithium salts / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alcohol / Aliphatic acyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid salt / Hydrocarbon derivative / Organic alkali metal salt / Organic lithium salt / Organic oxide / Organic oxygen compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- lithium salt (CHEBI:64735)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3655633623
- CAS number
- 919-16-4
- 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
References
- General References
- External Links
- ChemSpider
- 12932
- ChEBI
- 64735
- ChEMBL
- CHEMBL1201170
- Wikipedia
- Lithium_citrate
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count Not Available Completed Treatment Osteoporosis Pseudoglioma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral 8 meq/5mL Syrup Oral 8 meq/5mL Syrup Oral 8 mmol / 5 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 194.0 mg/mL ALOGPS logP -0.54 ALOGPS logP -1.3 Chemaxon logS -0.04 ALOGPS pKa (Strongest Acidic) 3.05 Chemaxon pKa (Strongest Basic) -4.2 Chemaxon Physiological Charge -3 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 140.62 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 68.14 m3·mol-1 Chemaxon Polarizability 14.23 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
Drug created at July 11, 2018 21:57 / Updated at December 05, 2023 12:31