Lithium carbonate
Identification
- Name
- Lithium carbonate
- Accession Number
- DB14509 (DBSALT001075)
- Type
- Small Molecule
- Groups
- Approved
- Description
- Not Available
- Structure
- Synonyms
- Carbonic acid, dilithium salt
- Dilithium carbonate
- Lithii carbonas
- Lithium carbonate
- Lithonate
- External IDs
- CP-15,467-61 / CP-15467-61 / CP-1546761
- Active Moieties
Name Kind UNII CAS InChI Key Lithium cation ionic 8H8Z5UER66 7439-93-2 HBBGRARXTFLTSG-UHFFFAOYSA-N - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Carbolith Cap 150mg Capsule 150 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1979-12-31 Not applicable Canada Carbolith Cap 300mg Capsule 300 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1971-12-31 Not applicable Canada Carbolith Capsules 600mg Capsule 600 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1992-12-31 Not applicable Canada Duralith Tab 300mg Tablet, extended release 300 mg Oral Janssen Pharmaceuticals 1985-12-31 2010-02-12 Canada Eskalith Capsule, gelatin coated 300 mg/1 Oral Physicians Total Care, Inc. 1970-04-06 2007-08-15 US Eskalith Capsule, gelatin coated 300 mg/1 Oral GlaxoSmithKline 2006-05-10 2007-06-25 US Eskalith CR Tablet, extended release 450 mg/1 Oral Physicians Total Care, Inc. 1982-03-29 2007-08-15 US Eskalith CR Tablet, extended release 450 mg/1 Oral GlaxoSmithKline 2006-05-10 2007-06-25 US Euro Lithium Capsule 300 mg Oral Euro Pharm International Canada Inc 2008-02-26 2013-07-10 Canada Euro Lithium Capsule 150 mg Oral Euro Pharm International Canada Inc 2008-02-26 2013-07-10 Canada - Generic Prescription Products
- International/Other Brands
- Eskalith / LithoTab
- Categories
- Acids
- Acids, Noncarboxylic
- Alkalies
- Anions
- Antimanic Agents
- Carbon Compounds, Inorganic
- Carbonates
- Carbonic Acid
- Central Nervous System Agents
- Central Nervous System Depressants
- Electrolytes
- Enzyme Inhibitors
- Ions
- Lithium Compounds
- Mood Stabilizer
- Narrow Therapeutic Index Drugs
- Psychotropic Drugs
- Tranquilizing Agents
- UNII
- 2BMD2GNA4V
- CAS number
- 554-13-2
- Weight
- Average: 73.89
Monoisotopic: 74.01675074 - Chemical Formula
- CLi2O3
- InChI Key
- XGZVUEUWXADBQD-UHFFFAOYSA-L
- InChI
- InChI=1S/CH2O3.2Li/c2-1(3)4;;/h(H2,2,3,4);;/q;2*+1/p-2
- IUPAC Name
- dilithium(1+) carbonate
- SMILES
- [Li+].[Li+].[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.
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
- Toxicity
- Not Available
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The risk or severity of adverse effects can be increased when Lithium carbonate is combined with (R)-warfarin. (S)-Warfarin The risk or severity of adverse effects can be increased when Lithium carbonate is combined with (S)-Warfarin. 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The serum concentration of Lithium carbonate can be increased when it is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 2,5-Dimethoxy-4-ethylamphetamine The therapeutic efficacy of 2,5-Dimethoxy-4-ethylamphetamine can be decreased when used in combination with Lithium carbonate. 2,5-Dimethoxy-4-ethylthioamphetamine The therapeutic efficacy of 2,5-Dimethoxy-4-ethylthioamphetamine can be decreased when used in combination with Lithium carbonate. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of Lithium carbonate can be decreased when it is combined with 3-isobutyl-1-methyl-7H-xanthine. 3,4-Methylenedioxyamphetamine The therapeutic efficacy of 3,4-Methylenedioxyamphetamine can be decreased when used in combination with Lithium carbonate. 4-Bromo-2,5-dimethoxyamphetamine The therapeutic efficacy of 4-Bromo-2,5-dimethoxyamphetamine can be decreased when used in combination with Lithium carbonate. 4-hydroxycoumarin The risk or severity of adverse effects can be increased when Lithium carbonate is combined with 4-hydroxycoumarin. 4-Methoxyamphetamine The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lithium carbonate. - Food Interactions
- Not Available
References
- General References
- 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]
- ILO: Lithium [Link]
- External Links
- KEGG Compound
- C07964
- ChemSpider
- 10654
- ChEBI
- 6504
- ChEMBL
- CHEMBL1200826
- Wikipedia
- Lithium_carbonate
- AHFS Codes
- 28:28.00 — Antimanic Agents
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Depression 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Capsule Oral 300 mg Capsule Oral 600 mg Capsule, gelatin coated Oral 300 mg/1 Tablet, extended release Oral 450 mg/1 Capsule Oral 150 mg Tablet Oral 300 mg/1 Solution Oral 8 meq/5mL Capsule Oral 150 mg/1 Capsule Oral 300 mg/1 Capsule Oral 600 mg/1 Capsule, gelatin coated Oral 150 mg/1 Capsule, gelatin coated Oral 600 mg/1 Tablet, extended release Oral 300 mg/1 Tablet, film coated, extended release Oral 300 mg/1 Tablet Oral 450 mg/1 Tablet, extended release Oral 300 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 644.0 mg/mL ALOGPS logP -0.28 ALOGPS logP 0.25 ChemAxon logS 0.94 ALOGPS pKa (Strongest Acidic) 6.05 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 63.19 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 31.17 m3·mol-1 ChemAxon Polarizability 3.52 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
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as organic carbonic acids. These are compounds comprising the carbonic acid functional group.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Organic carbonic acids and derivatives
- Sub Class
- Organic carbonic acids
- Direct Parent
- Organic carbonic acids
- Alternative Parents
- Carbonate salts / Organic lithium salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Carbonate salt / Carbonic acid / Organic lithium salt / Organic alkali metal salt / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Organooxygen compound / Carbonyl group
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- lithium salt, carbonate salt (CHEBI:6504)
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
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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 16:07 / Updated on February 19, 2019 08:59