Lithium carbonate

Identification

Name
Lithium carbonate
Accession Number
DB14509  (DBSALT001075)
Type
Small Molecule
Groups
Approved
Description
Not Available
Structure
Thumb
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
NameKindUNIICASInChI Key
Lithium cationionic8H8Z5UER667439-93-2HBBGRARXTFLTSG-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Carbolith Cap 150mgCapsule150 mgOralValeant Canada Lp Valeant Canada S.E.C.1979-12-31Not applicableCanada
Carbolith Cap 300mgCapsule300 mgOralValeant Canada Lp Valeant Canada S.E.C.1971-12-31Not applicableCanada
Carbolith Capsules 600mgCapsule600 mgOralValeant Canada Lp Valeant Canada S.E.C.1992-12-31Not applicableCanada
Duralith Tab 300mgTablet, extended release300 mgOralJanssen Pharmaceuticals1985-12-312010-02-12Canada
EskalithCapsule, gelatin coated300 mg/1OralGlaxoSmithKline2006-05-102007-06-25Us
EskalithCapsule, gelatin coated300 mg/1OralPhysicians Total Care, Inc.1970-04-062007-08-15Us
Eskalith CRTablet, extended release450 mg/1OralGlaxoSmithKline2006-05-102007-06-25Us
Eskalith CRTablet, extended release450 mg/1OralPhysicians Total Care, Inc.1982-03-292007-08-15Us
Euro LithiumCapsule300 mgOralEuro Pharm International Canada Inc2008-02-262013-07-10Canada
Euro LithiumCapsule150 mgOralEuro Pharm International Canada Inc2008-02-262013-07-10Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-lithium CarbonateCapsule300 mgOralApotex Corporation2001-02-12Not applicableCanada
Apo-lithium CarbonateCapsule150 mgOralApotex Corporation2001-02-12Not applicableCanada
Dom-lithium CarbonateCapsule300 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-lithium CarbonateCapsule600 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-lithium CarbonateCapsule150 mgOralDominion PharmacalNot applicableNot applicableCanada
Lithium CarbonateTablet, extended release450 mg/1OralMajor2003-06-172013-03-31Us
Lithium CarbonateCapsule150 mg/1OralCamber Pharmaceuticals2009-12-15Not applicableUs
Lithium carbonateTablet, film coated, extended release300 mg/1OralHeritage2013-03-30Not applicableUs
Lithium CarbonateCapsule150 mg/1OralTYA Pharmaceuticals2009-12-15Not applicableUs64725 054420180907 15195 iow9p5
Lithium CarbonateTablet, extended release300 mg/1OralAmerincan Health Packaging2014-10-01Not applicableUs
International/Other Brands
Eskalith / LithoTab
Categories
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.

TargetActionsOrganism
UInositol monophosphatase 2Not AvailableHuman
UInositol monophosphatase 1Not AvailableHuman
UGlycogen synthase kinase-3 betaNot AvailableHuman
UGlutamate receptor 3Not AvailableHuman
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
(R)-warfarinThe risk or severity of adverse effects can be increased when Lithium carbonate is combined with (R)-warfarin.
(S)-WarfarinThe 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 AcidThe 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-ethylamphetamineLithium carbonate may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Lithium carbonate.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of Lithium carbonate can be decreased when it is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Lithium carbonate.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Lithium carbonate.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Lithium carbonate is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lithium carbonate.
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
KEGG Compound
C07964
ChemSpider
10654
ChEBI
6504
ChEMBL
CHEMBL1200826
Wikipedia
Lithium_carbonate
AHFS Codes
  • 28:28.00 — Antimanic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentDepression1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral300 mg
CapsuleOral600 mg
Capsule, gelatin coatedOral300 mg/1
Tablet, extended releaseOral450 mg/1
CapsuleOral150 mg
TabletOral300 mg/1
SolutionOral8 meq/5mL
CapsuleOral150 mg/1
CapsuleOral300 mg/1
CapsuleOral600 mg/1
Capsule, gelatin coatedOral150 mg/1
Capsule, gelatin coatedOral600 mg/1
Tablet, extended releaseOral300 mg/1
Tablet, film coated, extended releaseOral300 mg/1
TabletOral450 mg/1
Tablet, extended releaseOral300 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility644.0 mg/mLALOGPS
logP-0.28ALOGPS
logP0.25ChemAxon
logS0.94ALOGPS
pKa (Strongest Acidic)6.05ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area63.19 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity31.17 m3·mol-1ChemAxon
Polarizability3.52 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

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
Human
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
Human
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
Human
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
Human
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 16:07 / Updated on December 16, 2018 07:02