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Identification
Name Lithium
Accession Number DB01356
Type small molecule
Groups approved
Description

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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Eskalith
LithoTab
Brand mixtures Not Available
Categories Not Available
CAS number 7439-93-2
Weight Average: 6.941
Monoisotopic: 7.016004049
Chemical Formula Li
InChI Key InChIKey=HBBGRARXTFLTSG-UHFFFAOYSA-N
InChI
InChI=1S/Li/q+1
Plain Text
IUPAC Name
lithium(1+) ion
SMILES
[Li+]
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Inorganic
Classes
  • Inorganic Ions and Gases
Substructures
  • Inorganic Ions and Gases
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.
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.
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
Pharmacoeconomics
Manufacturers
  • Noven therapeutics llc
  • Jds pharmaceuticals llc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Oral
Syrup Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Eskalith cr 450 mg tablet 0.8 USD tablet
Lithium Carbonate 450 mg Controlled Release Tabs 0.56 USD tab
Lithium Carbonate 300 mg Controlled Release Tabs 0.5 USD tab
Lithium Carbonate 600 mg capsule 0.44 USD capsule
Lithium Carbonate 300 mg capsule 0.29 USD capsule
Lithium Carbonate 300 mg tablet 0.29 USD tablet
Lithate 20 mg capsule 0.28 USD capsule
Lithium carb powder reagent 0.27 USD g
Lithium carbonate 300 mg tab 0.22 USD each
Lithium Carbonate 150 mg capsule 0.21 USD capsule
Lithium Citrate 8meq/5ml Syrup 0.15 USD ml
Lithium citrate 8 meq/5 ml sol 0.14 USD ml
Pms-Lithium Carbonate 600 mg Capsule 0.14 USD capsule
Carbolith 150 mg Capsule 0.13 USD capsule
Lithate 5 mg capsule 0.12 USD capsule
Lithane 150 mg Capsule 0.11 USD capsule
Lithane 300 mg Capsule 0.11 USD capsule
Carbolith 300 mg Capsule 0.1 USD capsule
Apo-Lithium Carbonate 150 mg Capsule 0.06 USD capsule
Apo-Lithium Carbonate 300 mg Capsule 0.06 USD capsule
Pms-Lithium Carbonate 150 mg Capsule 0.06 USD capsule
Pms-Lithium Carbonate 300 mg Capsule 0.06 USD capsule
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Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 0.512 g·cm −3 Not Available
Predicted Properties
Property Value Source
logP 0 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 0 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 0 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 0 ChemAxon
polarizability 1.78 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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. Epub 2010 May 7. Pubmed 20453535
External Links
Resource Link
KEGG Compound C15473 Link_out
PubChem Compound 28486 Link_out
PubChem Substance 46505392 Link_out
ChemSpider 26502 Link_out
ChEBI 49713 Link_out
ChEMBL 49713 Link_out
Therapeutic Targets Database DNC000879 Link_out
PharmGKB PA450243 Link_out
Drug Product Database 236683 Link_out
RxList http://www.rxlist.com/cgi/generic/lithium.htm Link_out
Drugs.com http://www.drugs.com/lithium.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Lithium Link_out
ATC Codes
  • N05AN01
  • D11AX04
AHFS Codes
  • 28:28.00
  • 92:02.00*
PDB Entries Not Available
FDA label show (200 KB)
MSDS show (72.1 KB)
Interactions
Drug Interactions
Drug Interaction
Aminophylline Theophylline decreases serum levels of lithium
Azilsartan medoxomil Azilsartan medoxomil may increase lithium serum concentrations.
Benazepril The ACE inhibitor increases serum levels of lithium
Bendroflumethiazide The thiazide diuretic, bendroflumethiazide, may increase serum levels of lithium.
Benzthiazide The thiazide diuretic, benzthiazide, may increase serum levels of lithium.
Caffeine Caffeine decreases serum levels of lithium
Candesartan The ARB increases serum levels of lithium
Captopril The ACE inhibitor increases serum levels of lithium
Celecoxib The COX-2 inhibitor increases serum levels of lithium
Chlorothiazide The thiazide diuretic, chlorothiazide, may increase serum levels of lithium.
Chlorthalidone The thiazide diuretic, chlorthalidone, may increase serum levels of lithium.
Cilazapril The ACE inhibitor increases serum levels of lithium
Citric Acid The urine alkalizer decreases the effect of lithium
Cyclothiazide The thiazide diuretic, cyclothiazide, may increase serum levels of lithium.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Diclofenac The NSAID, diclofenac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Diflunisal The NSAID, diflunisal, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Dyphylline Theophylline decreases serum levels of lithium
Enalapril The ACE inhibitor increases serum levels of lithium
Eplerenone Eplerenone increases serum levels of lithium
Eprosartan The ARB increases serum levels of lithium
Etoricoxib Etoricoxib increases serum levels of lithium
Fluoxetine The SSRI, fluoxetine, increases serum levels of lithium.
Fluvoxamine The SSRI, fluvoxamine, increases serum levels of lithium.
Forasartan The ARB increases serum levels of lithium
Fosinopril The ACE inhibitor increases serum levels of lithium
Haloperidol Possible extrapyramidal effects and neurotoxicity with this combination
Hydrochlorothiazide The thiazide diuretic, hydrochlorothiazide, may increase serum levels of lithium.
Hydroflumethiazide The thiazide diuretic, hydroflumethiazide, may increase serum levels of lithium.
Ibuprofen The NSAID, ibuprofen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Indapamide The thiazide diuretic, indapamide, may increase serum levels of lithium.
Indomethacin The NSAID, indomethacin, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Iodine Possible hypothyroidism with this combination
Irbesartan The ARB increases serum levels of lithium
Ketoprofen The NSAID, ketoprofen, may increase the serum concentration of lithium by decreasing its renal clearance. Consider a dose reduction in lithium upon initiation of ketoprofen therapy. Monitor for changes in the therapeutic and adverse effects of lithium if ketoprofen is initiated, discontinued or does changed.
Ketorolac The NSAID, ketorolac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Lisinopril The ACE inhibitor increases serum levels of lithium
Losartan Losartan increases serum levels of lithium
Lumiracoxib The COX-2 inhibitor increases serum levels of lithium
Mefenamic acid The NSAID, mefenamic acid, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Meloxicam Meloxicam increases serum levels of lithium
Methyclothiazide The thiazide diuretic, methyclothiazide, may increase serum levels of lithium.
Methyldopa Methyldopa may increase the adverse effects of lithium without affecting lithium serum levels. Monitor for signs and symptoms of lithium toxicity during concomitant therapy.
Metolazone The thiazide diuretic, metolazone, may increase serum levels of lithium.
Metronidazole Metronidazole increases the effect and toxicity of lithium
Moexipril The ACE inhibitor increases serum levels of lithium
Naproxen The NSAID, naproxen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Oxtriphylline Theophylline decreases serum levels of lithium
Perindopril The ACE inhibitor increases serum levels of lithium
Phenylbutazone The NSAID, phenylbutazone, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Piroxicam The NSAID, piroxicam, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Polythiazide The thiazide diuretic, polythiazide, may increase serum levels of lithium.
Potassium The urine alkalizer decreases the effect of lithium
Quinapril The ACE inhibitor increases serum levels of lithium
Quinethazone The thiazide diuretic, quinethazone, may increase serum levels of lithium.
Ramipril The ACE inhibitor increases serum levels of lithium
Rofecoxib The COX-2 inhibitor increases serum levels of lithium
Saprisartan The ARB increases serum levels of lithium
Sibutramine Possible serotoninergic syndrome with this combination
Sodium bicarbonate The urine alkalizer decreases the effect of lithium
Spirapril The ACE inhibitor increases serum levels of lithium
Sumatriptan Possible serotoninergic syndrome with this combination
Tasosartan The ARB increases serum levels of lithium
Telmisartan Telmisartan may increase serum Lithium concentrations. Monitor serum Lithium levels during concomitant therapy to avoid Lithium toxicity.
Tenoxicam Tenoxicam may increase the serum concentration of Lithium. A dose adjustment of Lithium may be required. Monitor for changes in Lithium therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed.
Tetrabenazine Inhibit biochemical and behavioural effects of tetrabenazine. Heed caution when using agents in combination.
Theophylline Theophylline decreases serum levels of lithium
Tiaprofenic acid Tiaprofenic acid may increase the therapeutic/adverse effects of Lithium by increasing Lithium serum concentrations. Monitor for changes in the therapeutic/adverse effects of Lithium if Tiaprofenic acid is initiated, discontinued or dose changed.
Tobramycin Increased risk of nephrotoxicity
Tolmetin Tolmetin may increase the risk of Lithium toxicity by decreasing the renal elminiation of Lithium. A dose adjustment of Lithium may be required. Monitor for changes in Lithium therapeutic and adverse effects if Tolmetin is initiated, discontinued or dose changed.
Topiramate Topiramate could modify lithium levels
Trandolapril Trandolapril may increase the serum concentration of Lithium increasing the risk of Lithium toxicity. Monitor for changes in Lithium serum concentrations, toxicity and efficacy if Trandolapril is initiated, discontinued or dose changed.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trichlormethiazide Trichlormethiazide may increase the serum concentration of Lithium by decreasing Lithium excretion. Monitor for changes in the therapeutic/adverse effects of Lithium if Trichlorthiazide is initiated, discontinued or dose changed.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Valdecoxib The COX-2 inhibitor increases serum levels of lithium
Valsartan Valsartan may increase serum lithium concentrations. Monitor serum lithium levels during concomitant therapy to avoid lithium toxicity.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Verapamil Signs of lithium toxicity
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and lithium, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid iodine supplements.
  • Do not change your salt intake from day to day without telling your doctor.
  • Take with food to reduce irritation. Drink plenty of liquids.
Targets

1. Glycogen synthase kinase-3 beta

Pharmacological action: unknown
Actions: inhibitor

Participates in the Wnt signaling pathway. Implicated in the hormonal control of several regulatory proteins including glycogen synthase, MYB and the transcription factor JUN. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA

Organism class: human
UniProt ID: P49841 Link_out
Gene: GSK3B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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 Jul 10;. Pubmed
  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. Pubmed

2. Inositol monophosphatase

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P29218 Link_out
Gene: IMPA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  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

3. Inositol monophosphatase 2

Pharmacological action: unknown
Actions: inhibitor

Myo-inositol phosphate + H(2)O = myo-inositol + phosphate

Organism class: human
UniProt ID: O14732 Link_out
Gene: IMPA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

4. Glutamate receptor 3

Pharmacological action: unknown
Actions: potentiator

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of GLU are mediated by a variety of receptors that are named according to their selective agonists

Organism class: human
UniProt ID: P42263 Link_out
Gene: GRIA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes
Searched, but no enzymes found.
Comments
Drug created on July 06, 2007 13:50 / Updated on April 22, 2013 16:10