Identification
- Summary
Lithium cation is a drug used for the management of bipolar disorder and other psychiatric conditions.
- Generic Name
- Lithium cation
- DrugBank Accession Number
- DB01356
- Background
Lithium was used during the 19th century to treat gout. Lithium salts such as lithium carbonate (Li2CO3), lithium citrate, and lithium orotate are mood stabilizers. They are used in the treatment of bipolar disorder, since unlike most other mood altering drugs, they counteract both mania and depression. Lithium can also be used to augment other antidepressant drugs. It is also sometimes prescribed as a preventive treatment for migraine disease and cluster headaches. The active principle in these salts is the lithium ion Li+, which having a smaller diameter, can easily displace K+ and Na+ and even Ca+2, in spite of its greater charge, occupying their sites in several critical neuronal enzymes and neurotransmitter receptors.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Lithium cation (DB01356)
- Weight
- Average: 6.941
Monoisotopic: 7.016004049 - Chemical Formula
- Li
- Synonyms
- Li(+)
- Lithium ion
- Lithium, ion
- Lithium, ion (li1+)
Pharmacology
- Indication
Lithium, in its salt forms, is used as a mood stabilizer and for the treatment of depression and mania. It is most frequently prescribed in the treatment of bipolar disorder.
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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 UGlycogen synthase kinase-3 beta inhibitorHumans UInositol monophosphatase 1 inhibitorHumans UInositol monophosphatase 2 inhibitorHumans UGlutamate receptor 3 potentiatorHumans - 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 software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Lithium cation is combined with 1,2-Benzodiazepine. Abacavir Lithium cation may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac The risk or severity of nephrotoxicity can be increased when Lithium cation is combined with Aceclofenac. Acemetacin The risk or severity of nephrotoxicity can be increased when Lithium cation is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Lithium cation is combined with Acenocoumarol. Acetaminophen Lithium cation may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Lithium cation. Acetophenazine The risk or severity of adverse effects can be increased when Lithium cation is combined with Acetophenazine. Acetylsalicylic acid The risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Lithium cation. Aclidinium Lithium cation may decrease the excretion rate of Aclidinium which could result in a higher serum level. 
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- Not Available
Products
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Categories
- Drug Categories
- Antidepressive Agents
- Antimanic Agents
- Antipsychotic Agents
- Central Nervous System Depressants
- Highest Risk QTc-Prolonging Agents
- Lithium Compounds
- Mood Stabilizer
- Nephrotoxic agents
- Neurotoxic agents
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of inorganic compounds known as homogeneous alkali metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a alkali metal atom.
- Kingdom
- Inorganic compounds
- Super Class
- Homogeneous metal compounds
- Class
- Homogeneous alkali metal compounds
- Sub Class
- Not Available
- Direct Parent
- Homogeneous alkali metal compounds
- Alternative Parents
- Not Available
- Substituents
- Homogeneous alkali metal
- Molecular Framework
- Not Available
- External Descriptors
- alkali metal cation, monovalent inorganic cation, monoatomic monocation (CHEBI:49713) / a cation (LI+)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8H8Z5UER66
- CAS number
- 7439-93-2
- InChI Key
- HBBGRARXTFLTSG-UHFFFAOYSA-N
- InChI
- InChI=1S/Li/q+1
- IUPAC Name
- lithium(1+) ion
- SMILES
- [Li+]
References
- Synthesis Reference
Jean-Paul Gabano, "Electrolyte for a lithium/thionyl chloride electric cell, a method of preparing said electrolyte and an electric cell which includes said electrolyte." U.S. Patent US4375502, issued 0000.
US4375502- General References
- External Links
- Human Metabolome Database
- HMDB0005949
- KEGG Compound
- C15473
- PubChem Compound
- 28486
- PubChem Substance
- 46505392
- ChemSpider
- 26502
- BindingDB
- 50259153
- 1546265
- ChEBI
- 49713
- ChEMBL
- CHEMBL1234004
- Therapeutic Targets Database
- DNC000879
- PharmGKB
- PA450243
- PDBe Ligand
- LI
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lithium
- PDB Entries
- 1dgd / 1e5k / 1h4c / 1h4d / 1h4e / 1hjj / 1hjl / 1knw / 1mgw / 1nqj … show 92 more
- FDA label
- Download (200 KB)
- MSDS
- Download (72.1 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Advanced Pharmaceutical Services Inc.
- Amerisource Health Services Corp.
- Anip Acquisition Co.
- Apotex Inc.
- Biotech Pharmaceuticals
- Cardinal Health
- Caremark LLC
- Comprehensive Consultant Services Inc.
- Coupler Enterprises Inc.
- Dept Health Central Pharmacy
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Glenmark Generics Ltd.
- Goldline Laboratories Inc.
- Heartland Repack Services LLC
- Hetero Drugs Ltd.
- Hikma Pharmaceuticals
- J T Baker
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Liberty Pharmaceuticals
- Major Pharmaceuticals
- Mckesson Corp.
- Murfreesboro Pharmaceutical Nursing Supply
- Neuman Distributors Inc.
- Noven Pharmaceuticals Inc.
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- Pharmacy Service Center
- Physicians Total Care Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Roxane Labs
- Sandhills Packaging Inc.
- Solvay Pharmaceuticals
- Southwood Pharmaceuticals
- Stat Rx Usa
- Sun Pharmaceutical Industries Ltd.
- Tya Pharmaceuticals
- UDL Laboratories
- Vangard Labs Inc.
- West-Ward Pharmaceuticals
- Dosage Forms
Form Route Strength Injection, solution Capsule Tablet Tablet, extended release - Prices
Unit description Cost Unit Eskalith cr 450 mg tablet 0.8USD tablet Lithium Carbonate 450 mg Controlled Release Tabs 0.56USD tab Lithium Carbonate 300 mg Controlled Release Tabs 0.5USD tab Lithium Carbonate 600 mg capsule 0.44USD capsule Lithium Carbonate 300 mg capsule 0.29USD capsule Lithium Carbonate 300 mg tablet 0.29USD tablet Lithate 20 mg capsule 0.28USD capsule Lithium carb powder reagent 0.27USD g Lithium carbonate 300 mg tab 0.22USD each Lithium Carbonate 150 mg capsule 0.21USD capsule Lithium Citrate 8meq/5ml Syrup 0.15USD ml Lithium citrate 8 meq/5 ml sol 0.14USD ml Pms-Lithium Carbonate 600 mg Capsule 0.14USD capsule Carbolith 150 mg Capsule 0.13USD capsule Lithate 5 mg capsule 0.12USD capsule Lithane 150 mg Capsule 0.11USD capsule Lithane 300 mg Capsule 0.11USD capsule Carbolith 300 mg Capsule 0.1USD capsule Apo-Lithium Carbonate 150 mg Capsule 0.06USD capsule Apo-Lithium Carbonate 300 mg Capsule 0.06USD capsule Pms-Lithium Carbonate 150 mg Capsule 0.06USD capsule Pms-Lithium Carbonate 300 mg Capsule 0.06USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 180.5 International Labour Organization boiling point (°C) 1336 International Labour Organization water solubility Violent reaction International Labour Organization - Predicted Properties
Property Value Source logP 0 Chemaxon pKa (Strongest Acidic) 3.09 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 0 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 0 m3·mol-1 Chemaxon Polarizability 1.78 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8382 Blood Brain Barrier + 0.9708 Caco-2 permeable + 0.7056 P-glycoprotein substrate Non-substrate 0.8831 P-glycoprotein inhibitor I Non-inhibitor 0.9869 P-glycoprotein inhibitor II Non-inhibitor 0.9855 Renal organic cation transporter Non-inhibitor 0.9199 CYP450 2C9 substrate Non-substrate 0.8465 CYP450 2D6 substrate Non-substrate 0.823 CYP450 3A4 substrate Non-substrate 0.8094 CYP450 1A2 substrate Non-inhibitor 0.8854 CYP450 2C9 inhibitor Non-inhibitor 0.9224 CYP450 2D6 inhibitor Non-inhibitor 0.9559 CYP450 2C19 inhibitor Non-inhibitor 0.9487 CYP450 3A4 inhibitor Non-inhibitor 0.9853 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9015 Ames test Non AMES toxic 0.9663 Carcinogenicity Carcinogens 0.623 Biodegradation Ready biodegradable 0.9031 Rat acute toxicity 2.0881 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9462 hERG inhibition (predictor II) Non-inhibitor 0.9716
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Actions
- Inhibitor
- 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
- Actions
- Inhibitor
- 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
- Actions
- Potentiator
- 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 06, 2007 19:50 / Updated at March 24, 2023 20:20