Lithium carbonate

Identification

Summary

Lithium carbonate is a medication used to treat manic episodes of bipolar disorder.

Brand Names
Carbolith, Lithane, Lithmax, Lithobid
Generic Name
Lithium carbonate
DrugBank Accession Number
DB14509
Background

Lithium has been used to treat manic episodes since the 19th century3. Though it is widely used, its mechanism of action is still unknownLabel1,3,4,6. Lithium carbonate has a narrow therapeutic range and so careful monitoring is required to avoid adverse effectsLabel.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 73.89
Monoisotopic: 74.01675074
Chemical Formula
CLi2O3
Synonyms
  • Carbonic acid, dilithium salt
  • Dilithium carbonate
  • Lithii carbonas
  • Lithium carbonate
  • Lithonate
External IDs
  • CP-15,467-61
  • CP-15467-61
  • CP-1546761

Pharmacology

Indication

Lithium is used as a mood stabilizer, and is indicated for the treatment of manic episodes and maintenance of bipolar disorderLabel.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Lithium's mechanism of action is still unknownLabel. 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 receptors3,4.

Mechanism of action

Lithium's mechanism of action is still unknownLabel. However, the “inositol depletion theory” suggests 3 main potential targets3. These targets are inositol monophosphatase, inositol polyphosphatase, and glycogen synthase kinase 3(GSK-3)3,6.

The “Inositol depletion theory” suggests lithium behaves as an uncompetitive inhibitor of inositol monophosphatase in a manner inversely proportional to the degree of stimulus3. This inhibition lowers levels of inositol triphosphate6. However, stronger inhibitors of inositol monophosphatase are not as clinically effective and low levels of inositol triphosphate are associated with memory impairment3,6.

Lithium acts on inositol polyphosphatase as an uncompetitive inhibitor3. This inhibition is thought to have multiple downstream effects that have yet to be clarified3.

Lithium regulates phosphorylation of GSK-3 which regulates other enzymes through phosphorylation3. Lithium can also inhibit GSK-3 through interfering with the magnesium ion in the active site3.

TargetActionsOrganism
UInositol monophosphatase 2Not AvailableHumans
UInositol monophosphatase 1Not AvailableHumans
UGlycogen synthase kinase-3 betaNot AvailableHumans
UGlutamate receptor 3Not AvailableHumans
Absorption

Lithium absorption is rapid and oral bioavailability is close to 100%2.

Volume of distribution

Apparent volume of distribution is 0.7 to 1.0L/kgLabel7.

Protein binding

Lithium carbonate is not significantly protein boundLabel2.

Metabolism

Lithium carbonate is not metabolized before excretionLabel.

Route of elimination

Lithium is primarily eliminated through the kidneys and elimination in the feces is insignificantLabel.

Half-life

The half life of lithium carbonate is 18 to 36 hoursLabel. Other sources say it may be 7 to 20 hours7.

Clearance

Clearance is generally between 10 and 40mL/min but may be as low as 15mL/min in elderly patients and those with renal impairment2.

Adverse Effects
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Toxicity

In rats, the oral LD50 is 525mg/kg and the inhalation LC50 is >2.17mg/L over 4 hoursMSDS.

There is insufficient data regarding the carcinogenicity, mutagenicity, or fertility impairment of lithium carbonateLabel. However, studies in rats and mice have shown repeated daily dosing of lithium carbonate result in adverse effects on male reproductive organs, spermatogenesis, and testosterone levelsLabel.

There is conflicting evidence regarding the incidence of cardiovascular abnormalities in first trimester administration of lithiumLabel. Animal studies have shown adverse effects on the fetus and fertility overallLabel. The risk and benefit of lithium use in pregnancy must be weighed and should lithium treatment continue in pregnancy, serum lithium concentrations should be regularly monitored, dosages should be adjusted, and lithium should be decreased or stopped 2 or 3 days before delivery to avoid maternal and/or neonatal toxicityLabel.

Breastfeeding is not recommended with maternal lithium use but if it is continued, the infant should be monitored for thyroid function and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changesLabel.

Safety in effectiveness in patients under 12 years has not been established, however dosing for patients 12 years and older is similar to that of adult patientsLabel.

Safety in geriatric patients has not been established, however caution is advised when using lithium as this population is more likely to have impaired renal functionLabel.

Patients with creatinine clearance between 30mL/min and 89mL/min should be started at a lower dose and slowly titrated to the correct dose while monitoring serum lithium levelsLabel. Patients with a creatinine clearance less than 30mL/min should not take lithium, especially in the case of a low sodium dietLabel.

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
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when 1,2-Benzodiazepine is combined with Lithium carbonate.
AbacavirAbacavir may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
AcenocoumarolThe risk or severity of adverse effects can be increased when Lithium carbonate is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
AcetazolamideThe absorption of Lithium carbonate can be decreased when combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Lithium carbonate.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Lithium carbonate which could result in a higher serum level.
Interactions
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Food Interactions
  • Avoid alcohol. Alcohol increased peak serum concentrations of lithium.
  • Avoid iodine-containing foods and supplements. Iodine and lithium may synergistically produce hypothyroidism.
  • Limit caffeine intake. Caffeine may decrease lithium concentrations.
  • Take with food. Food reduces gastrointestinal upset.

Products

Products
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Active Moieties
NameKindUNIICASInChI Key
Lithium cationionic8H8Z5UER667439-93-2HBBGRARXTFLTSG-UHFFFAOYSA-N
Product Images
International/Other Brands
LithoTab
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CarbolithCapsule150 mgOralBausch Health, Canada Inc.1979-12-31Not applicableCanada flag
CarbolithCapsule600 mgOralBausch Health, Canada Inc.1992-12-31Not applicableCanada flag
CarbolithCapsule300 mgOralBausch Health, Canada Inc.1971-12-31Not applicableCanada flag
Duralith Tab 300mgTablet, extended release300 mgOralJanssen Pharmaceuticals1985-12-312010-02-12Canada flag
EskalithCapsule, gelatin coated300 mg/1OralPhysicians Total Care, Inc.1970-04-062007-08-15US flag
EskalithCapsule, gelatin coated300 mg/1OralGlaxoSmithKline2006-05-102007-06-25US flag
Eskalith CRTablet, extended release450 mg/1OralGlaxoSmithKline2006-05-102007-06-25US flag
Eskalith CRTablet, extended release450 mg/1OralPhysicians Total Care, Inc.1982-03-292007-08-15US flag
LithaneTablet300 mg/1OralMiles Pharmaceuticals2006-06-12Not applicableUS flag
LithaneCapsule150 mgOralErfa Canada 2012 Inc1993-12-31Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-lithium CarbonateCapsule300 mgOralApotex Corporation2001-02-12Not applicableCanada flag
Apo-lithium CarbonateCapsule150 mgOralApotex Corporation2001-02-12Not applicableCanada flag
Dom-lithium CarbonateCapsule150 mg / capOralDominion PharmacalNot applicableNot applicableCanada flag
Dom-lithium CarbonateCapsule600 mg / capOralDominion PharmacalNot applicableNot applicableCanada flag
Dom-lithium CarbonateCapsule300 mg / capOralDominion PharmacalNot applicableNot applicableCanada flag
Euro LithiumCapsule300 mgOralEuro Pharm International Canada Inc2008-02-262013-07-10Canada flag
Euro LithiumCapsule150 mgOralEuro Pharm International Canada Inc2008-02-262013-07-10Canada flag
Lithium CarbonateCapsule300 mg/1OralPhysicians Total Care, Inc.1995-01-16Not applicableUS flag54868 133520180907 15195 1bgxsme
Lithium CarbonateCapsule300 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
Lithium CarbonateTablet, film coated, extended release300 mg/1OralREMEDYREPACK INC.2017-07-192020-04-07US flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic acyclic compound / Carbonate salt / Carbonic acid / Carbonyl group / Hydrocarbon derivative / Organic alkali metal salt / Organic lithium salt / Organic oxide / Organic oxygen compound / Organic salt
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
lithium salt, carbonate salt (CHEBI:6504)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
2BMD2GNA4V
CAS number
554-13-2
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

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. [Article]
  2. Hedya SA, Swoboda HD: Lithium Toxicity . [Article]
  3. Serretti A, Drago A, De Ronchi D: Lithium pharmacodynamics and pharmacogenetics: focus on inositol mono phosphatase (IMPase), inositol poliphosphatase (IPPase) and glycogen sinthase kinase 3 beta (GSK-3 beta). Curr Med Chem. 2009;16(15):1917-48. [Article]
  4. Chalecka-Franaszek E, Chuang DM: Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8745-50. [Article]
  5. ILO: Lithium [Link]
  6. Bipolar Disorders and Lithium: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Indications of Lithium: Review of Articles [Link]
  7. New Zealand Drug Data Sheet: Lithium Carbonate [Link]
KEGG Compound
C07964
ChemSpider
10654
ChEBI
6504
ChEMBL
CHEMBL1200826
Wikipedia
Lithium_carbonate
FDA label
Download (487 KB)
MSDS
Download (51 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceBipolar Disorder (BD)1
4CompletedDiagnosticAsthma / Major Depressive Disorder (MDD)1
4CompletedDiagnosticBipolar Disorder (BD)1
4CompletedPreventionDepression, Bipolar1
4CompletedTreatmentAcute Mania1
4CompletedTreatmentAcute Mania in Bipolar Disorder1
4CompletedTreatmentBipolar 1 Disorder1
4CompletedTreatmentBipolar 1 Disorder / Bipolar Disorder, Type II1
4CompletedTreatmentBipolar Disorder (BD)9
4CompletedTreatmentBipolar Disorder (BD) / Depression2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Capsule, liquid filledOral300 mg
Tablet, film coatedOral
CapsuleOral600 mg
CapsuleOral
CapsuleOral150 MG
CapsuleOral300 MG
Tablet, film coatedOral450 mg
Capsule, gelatin coatedOral300 mg/1
Tablet, extended releaseOral450 mg/1
Tablet, extended releaseOral400 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
CapsuleOral150 mg / cap
CapsuleOral300 mg / cap
Tablet, extended releaseOral300 mg
TabletOral400 mg
TabletOral
CapsuleOral600 mg / cap
Tablet, film coatedOral
Tablet, extended releaseOral450 mg
TabletOral250 mg
TabletOral300 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
PropertyValueSource
melting point (°C)180.5http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0710
boiling point (°C)1336http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0710
water solubility100mMhttp://www.chemspider.com/Chemical-Structure.10654.html
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

Targets

Drugtargets
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ww domain binding
Specific Function
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical...
Gene Name
SCNN1A
Uniprot ID
P37088
Uniprot Name
Amiloride-sensitive sodium channel subunit alpha
Molecular Weight
75703.08 Da
References
  1. Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E: alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol. 2011 Feb;22(2):253-61. doi: 10.1681/ASN.2010070734. Epub 2010 Nov 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ww domain binding
Specific Function
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical...
Gene Name
SCNN1B
Uniprot ID
P51168
Uniprot Name
Amiloride-sensitive sodium channel subunit beta
Molecular Weight
72658.485 Da
References
  1. Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E: alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol. 2011 Feb;22(2):253-61. doi: 10.1681/ASN.2010070734. Epub 2010 Nov 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ww domain binding
Specific Function
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical...
Gene Name
SCNN1G
Uniprot ID
P51170
Uniprot Name
Amiloride-sensitive sodium channel subunit gamma
Molecular Weight
74269.62 Da
References
  1. Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E: alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol. 2011 Feb;22(2):253-61. doi: 10.1681/ASN.2010070734. Epub 2010 Nov 4. [Article]

Drug created on July 11, 2018 22:07 / Updated on July 24, 2021 14:58