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Identification
NameLithium
Accession NumberDB01356
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
Li(+)Not AvailableNot Available
Lithium cationNot AvailableNot Available
LITHIUM ionNot AvailableNot Available
Lithium, ionNot AvailableNot Available
Lithium, ion (li1+)Not AvailableNot Available
Salts
Name/CAS Structure Properties
Lithium carbonate
Thumb Not applicable DBSALT001075
Brand names
NameCompany
EskalithNot Available
LITHOBIDNot Available
LithoTabNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number7439-93-2
WeightAverage: 6.941
Monoisotopic: 7.016004049
Chemical FormulaLi
InChI KeyHBBGRARXTFLTSG-UHFFFAOYSA-N
InChI
InChI=1S/Li/q+1
IUPAC Name
lithium(1+) ion
SMILES
[Li+]
Mass SpecNot Available
Taxonomy
KingdomInorganic Compounds
SuperclassHomogeneous Metal Compounds
ClassHomogeneous Alkali Metal Compounds
SubclassNot Available
Direct parentHomogeneous Alkali Metal Compounds
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionThis compound belongs to the homogeneous alkali metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a alkali metal atom.
Pharmacology
IndicationLithium is used as a mood stabilizer, and is used for treatment of depression and mania. It is often used in bipolar disorder treatment.
PharmacodynamicsAlthough 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 actionThe 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.9224
CYP450 2D6 substrate Non-inhibitor 0.9559
CYP450 2C19 substrate Non-inhibitor 0.9487
CYP450 3A4 substrate 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
Pharmacoeconomics
Manufacturers
  • Noven therapeutics llc
  • Jds pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
LiquidOral
SyrupOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Eskalith cr 450 mg tablet0.8USDtablet
Lithium Carbonate 450 mg Controlled Release Tabs0.56USDtab
Lithium Carbonate 300 mg Controlled Release Tabs0.5USDtab
Lithium Carbonate 600 mg capsule0.44USDcapsule
Lithium Carbonate 300 mg capsule0.29USDcapsule
Lithium Carbonate 300 mg tablet0.29USDtablet
Lithate 20 mg capsule0.28USDcapsule
Lithium carb powder reagent0.27USDg
Lithium carbonate 300 mg tab0.22USDeach
Lithium Carbonate 150 mg capsule0.21USDcapsule
Lithium Citrate 8meq/5ml Syrup0.15USDml
Lithium citrate 8 meq/5 ml sol0.14USDml
Pms-Lithium Carbonate 600 mg Capsule0.14USDcapsule
Carbolith 150 mg Capsule0.13USDcapsule
Lithate 5 mg capsule0.12USDcapsule
Lithane 150 mg Capsule0.11USDcapsule
Lithane 300 mg Capsule0.11USDcapsule
Carbolith 300 mg Capsule0.1USDcapsule
Apo-Lithium Carbonate 150 mg Capsule0.06USDcapsule
Apo-Lithium Carbonate 300 mg Capsule0.06USDcapsule
Pms-Lithium Carbonate 150 mg Capsule0.06USDcapsule
Pms-Lithium Carbonate 300 mg Capsule0.06USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point0.512 g·cm −3Not Available
Predicted Properties
PropertyValueSource
logP0ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m3·mol-1ChemAxon
Polarizability1.78 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
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 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
ResourceLink
KEGG CompoundC15473
PubChem Compound28486
PubChem Substance46505392
ChemSpider26502
ChEBI49713
ChEMBLCHEMBL2146126
Therapeutic Targets DatabaseDNC000879
PharmGKBPA450243
Drug Product Database236683
RxListhttp://www.rxlist.com/cgi/generic/lithium.htm
Drugs.comhttp://www.drugs.com/lithium.html
WikipediaLithium
ATC CodesN05AN01D11AX04
AHFS Codes
  • 28:28.00
  • 92:02.00*
PDB EntriesNot Available
FDA labelshow(200 KB)
MSDSshow(72.1 KB)
Interactions
Drug Interactions
Drug
AminophyllineTheophylline decreases serum levels of lithium
Azilsartan medoxomilAzilsartan medoxomil may increase lithium serum concentrations.
BenazeprilThe ACE inhibitor increases serum levels of lithium
BendroflumethiazideThe thiazide diuretic, bendroflumethiazide, may increase serum levels of lithium.
BenzthiazideThe thiazide diuretic, benzthiazide, may increase serum levels of lithium.
CaffeineCaffeine decreases serum levels of lithium
CandesartanThe ARB increases serum levels of lithium
CaptoprilThe ACE inhibitor increases serum levels of lithium
CelecoxibThe COX-2 inhibitor increases serum levels of lithium
ChlorothiazideThe thiazide diuretic, chlorothiazide, may increase serum levels of lithium.
ChlorthalidoneThe thiazide diuretic, chlorthalidone, may increase serum levels of lithium.
CilazaprilThe ACE inhibitor increases serum levels of lithium
Citric AcidThe urine alkalizer decreases the effect of lithium
CyclothiazideThe thiazide diuretic, cyclothiazide, may increase serum levels of lithium.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DiclofenacThe NSAID, diclofenac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
DiflunisalThe NSAID, diflunisal, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
DyphyllineTheophylline decreases serum levels of lithium
EnalaprilThe ACE inhibitor increases serum levels of lithium
EplerenoneEplerenone increases serum levels of lithium
EprosartanThe ARB increases serum levels of lithium
EtoricoxibEtoricoxib increases serum levels of lithium
FluoxetineThe SSRI, fluoxetine, increases serum levels of lithium.
FluvoxamineThe SSRI, fluvoxamine, increases serum levels of lithium.
ForasartanThe ARB increases serum levels of lithium
FosinoprilThe ACE inhibitor increases serum levels of lithium
HaloperidolPossible extrapyramidal effects and neurotoxicity with this combination
HydrochlorothiazideThe thiazide diuretic, hydrochlorothiazide, may increase serum levels of lithium.
HydroflumethiazideThe thiazide diuretic, hydroflumethiazide, may increase serum levels of lithium.
IbuprofenThe NSAID, ibuprofen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
IndapamideThe thiazide diuretic, indapamide, may increase serum levels of lithium.
IndomethacinThe NSAID, indomethacin, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
IodinePossible hypothyroidism with this combination
IrbesartanThe ARB increases serum levels of lithium
KetoprofenThe 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.
KetorolacThe NSAID, ketorolac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
LisinoprilThe ACE inhibitor increases serum levels of lithium
LosartanLosartan increases serum levels of lithium
LumiracoxibThe COX-2 inhibitor increases serum levels of lithium
Mefenamic acidThe NSAID, mefenamic acid, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
MeloxicamMeloxicam increases serum levels of lithium
MethyclothiazideThe thiazide diuretic, methyclothiazide, may increase serum levels of lithium.
MethyldopaMethyldopa may increase the adverse effects of lithium without affecting lithium serum levels. Monitor for signs and symptoms of lithium toxicity during concomitant therapy.
MetolazoneThe thiazide diuretic, metolazone, may increase serum levels of lithium.
MetronidazoleMetronidazole increases the effect and toxicity of lithium
MoexiprilThe ACE inhibitor increases serum levels of lithium
NaproxenThe NSAID, naproxen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
OxtriphyllineTheophylline decreases serum levels of lithium
PerindoprilThe ACE inhibitor increases serum levels of lithium
PhenylbutazoneThe NSAID, phenylbutazone, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
PiroxicamThe NSAID, piroxicam, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
PolythiazideThe thiazide diuretic, polythiazide, may increase serum levels of lithium.
PotassiumThe urine alkalizer decreases the effect of lithium
QuinaprilThe ACE inhibitor increases serum levels of lithium
QuinethazoneThe thiazide diuretic, quinethazone, may increase serum levels of lithium.
RamiprilThe ACE inhibitor increases serum levels of lithium
RofecoxibThe COX-2 inhibitor increases serum levels of lithium
Salmon CalcitoninMonitor therapy because calcitonin may reduce the serum concentration of lithium.
SaprisartanThe ARB increases serum levels of lithium
SibutraminePossible serotoninergic syndrome with this combination
Sodium bicarbonateThe urine alkalizer decreases the effect of lithium
SpiraprilThe ACE inhibitor increases serum levels of lithium
SumatriptanPossible serotoninergic syndrome with this combination
TasosartanThe ARB increases serum levels of lithium
TelmisartanTelmisartan may increase serum Lithium concentrations. Monitor serum Lithium levels during concomitant therapy to avoid Lithium toxicity.
TenoxicamTenoxicam 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.
TetrabenazineInhibit biochemical and behavioural effects of tetrabenazine. Heed caution when using agents in combination.
TheophyllineTheophylline decreases serum levels of lithium
Tiaprofenic acidTiaprofenic 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.
TobramycinIncreased risk of nephrotoxicity
TolmetinTolmetin 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.
TopiramateTopiramate could modify lithium levels
TrandolaprilTrandolapril 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.
TranylcypromineIncreased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrichlormethiazideTrichlormethiazide 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.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ValdecoxibThe COX-2 inhibitor increases serum levels of lithium
ValsartanValsartan may increase serum lithium concentrations. Monitor serum lithium levels during concomitant therapy to avoid lithium toxicity.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VerapamilSigns of lithium toxicity
ZolmitriptanUse 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Glycogen synthase kinase-3 beta P49841 Details

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 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inositol monophosphatase 1 P29218 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inositol monophosphatase 2 O14732 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: potentiator

Components

Name UniProt ID Details
Glutamate receptor 3 P42263 Details

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

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Drug created on July 06, 2007 13:50 / Updated on September 16, 2013 17:14