Identification

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Name
Lithium cation
Accession Number
DB01356
Type
Small Molecule
Groups
Experimental
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
  • Li(+)
  • Lithium ion
  • Lithium, ion
  • Lithium, ion (li1+)
Categories
UNII
8H8Z5UER66
CAS number
7439-93-2
Weight
Average: 6.941
Monoisotopic: 7.016004049
Chemical Formula
Li
InChI Key
HBBGRARXTFLTSG-UHFFFAOYSA-N
InChI
InChI=1S/Li/q+1
IUPAC Name
lithium(1+) ion
SMILES
[Li+]

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
UGlycogen synthase kinase-3 beta
inhibitor
Humans
UInositol monophosphatase 1
inhibitor
Humans
UInositol monophosphatase 2
inhibitor
Humans
UGlutamate receptor 3
potentiator
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
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.
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Lithium cation is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Lithium cation is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of 2,5-Dimethoxy-4-ethylamphetamine can be decreased when used in combination with Lithium cation.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of 2,5-Dimethoxy-4-ethylthioamphetamine can be decreased when used in combination with Lithium cation.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of Lithium cation can be decreased when it is combined with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of 4-Bromo-2,5-dimethoxyamphetamine can be decreased when used in combination with Lithium cation.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Lithium cation is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Lithium cation is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Lithium cation is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe serum concentration of Lithium cation can be decreased when it is combined with 6-O-benzylguanine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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.

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
  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
Human Metabolome Database
HMDB0005949
KEGG Compound
C15473
PubChem Compound
28486
PubChem Substance
46505392
ChemSpider
26502
ChEBI
49713
ChEMBL
CHEMBL1234004
Therapeutic Targets Database
DNC000879
PharmGKB
PA450243
HET
LI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lithium
AHFS Codes
  • 28:28.00 — Antimanic Agents
PDB Entries
1dgd / 1e5k / 1h4c / 1h4d / 1h4e / 1hjj / 1hjl / 1knw / 1mgw / 1nqj
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FDA label
Download (200 KB)
MSDS
Download (72.1 KB)

Clinical Trials

Clinical Trials
Not Available

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
Not Available
Prices
Unit descriptionCostUnit
Eskalith cr 450 mg tablet0.8USD tablet
Lithium Carbonate 450 mg Controlled Release Tabs0.56USD tab
Lithium Carbonate 300 mg Controlled Release Tabs0.5USD tab
Lithium Carbonate 600 mg capsule0.44USD capsule
Lithium Carbonate 300 mg capsule0.29USD capsule
Lithium Carbonate 300 mg tablet0.29USD tablet
Lithate 20 mg capsule0.28USD capsule
Lithium carb powder reagent0.27USD g
Lithium carbonate 300 mg tab0.22USD each
Lithium Carbonate 150 mg capsule0.21USD capsule
Lithium Citrate 8meq/5ml Syrup0.15USD ml
Lithium citrate 8 meq/5 ml sol0.14USD ml
Pms-Lithium Carbonate 600 mg Capsule0.14USD capsule
Carbolith 150 mg Capsule0.13USD capsule
Lithate 5 mg capsule0.12USD capsule
Lithane 150 mg Capsule0.11USD capsule
Lithane 300 mg Capsule0.11USD capsule
Carbolith 300 mg Capsule0.1USD capsule
Apo-Lithium Carbonate 150 mg Capsule0.06USD capsule
Apo-Lithium Carbonate 300 mg Capsule0.06USD capsule
Pms-Lithium Carbonate 150 mg Capsule0.06USD capsule
Pms-Lithium Carbonate 300 mg Capsule0.06USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180.5International Labour Organization
boiling point (°C)1336International Labour Organization
water solubilityViolent reactionInternational Labour Organization
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8382
Blood Brain Barrier+0.9708
Caco-2 permeable+0.7056
P-glycoprotein substrateNon-substrate0.8831
P-glycoprotein inhibitor INon-inhibitor0.9869
P-glycoprotein inhibitor IINon-inhibitor0.9855
Renal organic cation transporterNon-inhibitor0.9199
CYP450 2C9 substrateNon-substrate0.8465
CYP450 2D6 substrateNon-substrate0.823
CYP450 3A4 substrateNon-substrate0.8094
CYP450 1A2 substrateNon-inhibitor0.8854
CYP450 2C9 inhibitorNon-inhibitor0.9224
CYP450 2D6 inhibitorNon-inhibitor0.9559
CYP450 2C19 inhibitorNon-inhibitor0.9487
CYP450 3A4 inhibitorNon-inhibitor0.9853
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9015
Ames testNon AMES toxic0.9663
CarcinogenicityCarcinogens 0.623
BiodegradationReady biodegradable0.9031
Rat acute toxicity2.0881 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9462
hERG inhibition (predictor II)Non-inhibitor0.9716
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-d37172edddcf6ff27879
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-d37172edddcf6ff27879
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-d37172edddcf6ff27879
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d

Taxonomy

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+)

Targets

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
  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
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
  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
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
  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
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
  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 06, 2007 13:50 / Updated on October 17, 2019 21:28