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Lithium Carbonate
Also known as: 554-13-2, Dilithium carbonate, Lithonate, Lithobid, Lithane, Carbonic acid, dilithium salt
Molecular Formula
CLi2O3
Molecular Weight
73.9  g/mol
InChI Key
XGZVUEUWXADBQD-UHFFFAOYSA-L
FDA UNII
2BMD2GNA4V

A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems.
1 2D Structure

Lithium Carbonate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
dilithium;carbonate
2.1.2 InChI
InChI=1S/CH2O3.2Li/c2-1(3)4;;/h(H2,2,3,4);;/q;2*+1/p-2
2.1.3 InChI Key
XGZVUEUWXADBQD-UHFFFAOYSA-L
2.1.4 Canonical SMILES
[Li+].[Li+].C(=O)([O-])[O-]
2.2 Other Identifiers
2.2.1 UNII
2BMD2GNA4V
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Bicarbonate, Lithium

2. Carbonate, Dilithium

3. Carbonate, Lithium

4. Cp 15,467 61

5. Cp-15,467-61

6. Cp15,46761

7. Dilithium Carbonate

8. Eskalith

9. Lithane

10. Lithium Bicarbonate

11. Lithobid

12. Lithonate

13. Lithotabs

14. Micalith

15. Nsc 16895

16. Nsc-16895

17. Nsc16895

18. Priadel

19. Quilinorm Retard

20. Quilinorm-retard

21. Quilinormretard

2.3.2 Depositor-Supplied Synonyms

1. 554-13-2

2. Dilithium Carbonate

3. Lithonate

4. Lithobid

5. Lithane

6. Carbonic Acid, Dilithium Salt

7. Eskalith

8. Lithotabs

9. Carbonic Acid Lithium Salt

10. Liskonum

11. Lithizine

12. Micalith

13. Priadel

14. Limas

15. Eskalith Cr

16. Camcolit

17. Carbolitium

18. Neurolepsin

19. Lithium Carbonicum

20. Nsc-16895

21. Candamide

22. Carbolith

23. Eutimin

24. Hypnorex

25. Lithicarb

26. Lithinate

27. Lithionate

28. Liticar

29. Manialith

30. Maniprex

31. Litard

32. Lithea

33. Plenur

34. Quilonum Retard

35. Pfi-lithium

36. Lithium Phasal

37. Pfl-lithium

38. Litho-carb

39. Cp-15467-61

40. Lithium Carbonate (li2co3)

41. Cp-15,467-61

42. Mfcd00011084

43. 2bmd2gna4v

44. Chebi:6504

45. Carbonic Acid Lithium Salt (li2co3)

46. Lithium Carbonate (2:1)

47. Cp 15467-61

48. Ceglution

49. Phasal

50. Cp-1546761

51. Teralithe [french]

52. Lithium Carbonate Nanoparticles

53. Carbolithium

54. Teralithe

55. Lithium, Reference Standard Solution

56. Dilithium;carbonate

57. Li2 (c O3)

58. Carbonic Acid Dilithium Salt

59. Ccris 3153

60. Hsdb 3351

61. Einecs 209-062-5

62. Unii-2bmd2gna4v

63. Carbolithium Ifi

64. Lithium Qd

65. Eskalith (tn)

66. Lithobid (tn)

67. Lithium Carbonate [usan:usp:jan]

68. Starbld0023766

69. Lithium Carbonate Powder

70. Li2co3

71. Dilithium Trioxidocarbonate

72. Ec 209-062-5

73. Lithium Carbonate [mi]

74. Lithium Carbonate [jan]

75. Chembl1200826

76. Dtxsid1023784

77. Lithium Carbonate (jp17/usp)

78. Lithium Carbonate [hsdb]

79. Lithium Carbonate [inci]

80. Lithium Carbonate [usan]

81. Lithium Carbonate [vandf]

82. Lithium Carbonicum [hpus]

83. Lithium Carbonate [mart.]

84. Lithium Carbonate [usp-rs]

85. Lithium Carbonate [who-dd]

86. Lithium Carbonate [who-ip]

87. Str02638

88. Carbonic Acid, Lithium Salt (1:2)

89. Dilithium Carbonate [who-ip]

90. Lithium Carbonate, Acs Reagent Grade

91. Akos015904647

92. Angc-554-13-2

93. Db14509

94. Lithii Carbonas [who-ip Latin]

95. Lithium Carbonate [orange Book]

96. Lithium Carbonate [ep Monograph]

97. Lithium Carbonate [usp Monograph]

98. B7705

99. Ft-0627895

100. L0224

101. C07964

102. D00801

103. Dilithium Carbonate, Dilithium Salt, Carbonic Acid

104. Q410174

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 73.9 g/mol
Molecular Formula CLi2O3
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count3
Rotatable Bond Count0
Exact Mass74.01675073 g/mol
Monoisotopic Mass74.01675073 g/mol
Topological Polar Surface Area63.2 Ų
Heavy Atom Count6
Formal Charge0
Complexity18.8
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count3
4 Drug and Medication Information
4.1 Drug Information
1 of 4  
Drug NameLithium carbonate
Drug LabelEach capsule for oral administration contains 150 mg, 300 mg or 600 mg of Lithium Carbonate USP.Inactive IngredientsThe capsules contain talc. The hard gelatin shell consists of gelatin, titanium dioxide, sodium lauryl sulphate and FD & C Red 40.The..
Active IngredientLithium carbonate
Dosage FormTablet, extended release; Tablet; Capsule
RouteOral
Strength150mg; 600mg; 300mg; 450mg
Market StatusPrescription
CompanyMylan Pharms; Alembic; Hetero Labs Ltd Iii; Sun Pharm Inds; Hikma Pharms; Roxane; Glenmark Generics

2 of 4  
Drug NameLithobid
Drug LabelLITHOBID tablets contain lithium carbonate, a white odorless alkaline powder with molecular formula Li2CO3 and molecular weight 73.89. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at...
Active IngredientLithium carbonate
Dosage FormTablet, extended release
RouteOral
Strength300mg
Market StatusPrescription
CompanyAni Pharms

3 of 4  
Drug NameLithium carbonate
Drug LabelEach capsule for oral administration contains 150 mg, 300 mg or 600 mg of Lithium Carbonate USP.Inactive IngredientsThe capsules contain talc. The hard gelatin shell consists of gelatin, titanium dioxide, sodium lauryl sulphate and FD & C Red 40.The..
Active IngredientLithium carbonate
Dosage FormTablet, extended release; Tablet; Capsule
RouteOral
Strength150mg; 600mg; 300mg; 450mg
Market StatusPrescription
CompanyMylan Pharms; Alembic; Hetero Labs Ltd Iii; Sun Pharm Inds; Hikma Pharms; Roxane; Glenmark Generics

4 of 4  
Drug NameLithobid
Drug LabelLITHOBID tablets contain lithium carbonate, a white odorless alkaline powder with molecular formula Li2CO3 and molecular weight 73.89. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at...
Active IngredientLithium carbonate
Dosage FormTablet, extended release
RouteOral
Strength300mg
Market StatusPrescription
CompanyAni Pharms

4.2 Therapeutic Uses

Antidepressive Agents; Antimanic Agents; Antithyroid Agents; Enzyme Inhibitors

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


Most prepn currently used in the U.S. are tablets or capsules of lithium carbonate. Slow-release prepn of lithium carbonate also are available, as is a liq prepn of lithium citrate (with 8 mEq of Li+, equivalent to 300 mg of carbonate salt, per 5 mL or 1 teaspoonful of citrate liq). Salts other than the carbonate have been used, but the carbonate salt is favored for tablets and capsules because it is relatively less hygroscopic and less irritating to the gut than other salts, especially the chloride salt. /Li therapy/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 511


Lithium /carbonate and citrate/ is indicated as the primary agent in the treatment of acute manic and hypomanic episodes in bipolar disorder, and for maintenance therapy to help diminish the intensity and frequency of subsequent manic episodes in patients with a history of mania. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1844


Lithium /carbonate and citrate/ is used in some patients as the agent of choice in the prevention of bipolar depression. Clinicians have observed a diminished intensity and frequency of severe depressive episodes. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1844


For more Therapeutic Uses (Complete) data for LITHIUM CARBONATE (28 total), please visit the HSDB record page.


4.3 Drug Warning

Because of potential effects of lithium upon thyroid and renal function, appropriate indices of these functions should be measured prior to start of treatment, then monitored periodically as therapy proceeds.

Miller, R. R., and D. J. Greenblatt. Handbook of Drug Therapy. New York: Elsevier North Holland, 1979., p. 580


Lithium carbonate should not be used in patients with cardiovascular or renal disease. ...Should not be used in children under 12 yr of age.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1025


Outpatients and their families should be warned that the patient must discontinue lithium therapy immediately and consult a physician if signs of lithium intoxication such as muscle twitching, tremor, mild ataxia, drowsiness, muscle weakness, diarrhea, or vomiting occur. Patients also should be warned that lithium may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2570


Lithium should be used cautiously in patients with preexisting cardiovascular or thyroid disease. Patients with underlying cardiovascular disease should be observed carefully for signs and symptoms of arrhythmia (including periodic ECG determinations), and serum lithium concentrations should be kept within the therapeutic range since nodal arrhythmias may occur. Patients with underlying hypothyroidism should have thyroid function (T3, T4, and TSH concentrations) evaluated yearly and be given supplemental thyroid therapy when needed.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2571


For more Drug Warnings (Complete) data for LITHIUM CARBONATE (45 total), please visit the HSDB record page.


4.4 Drug Indication

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


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

Lithium's 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.


5.2 MeSH Pharmacological Classification

Antidepressive Agents

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. (See all compounds classified as Antidepressive Agents.)


Enzyme Inhibitors

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)


Antimanic Agents

Agents that are used to treat bipolar disorders or mania associated with other affective disorders. (See all compounds classified as Antimanic Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Pharmacological Classes
Mood Stabilizer [EPC]
5.4 Absorption, Distribution and Excretion

Absorption

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


Route of Elimination

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


Volume of Distribution

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


Clearance

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


... Lithium /carbonate/ crosses placenta and is present in mother and fetus in same concentration.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 313


Lithium /carbonate/ is completely absorbed six to eight hours after oral administration. Since the onset of action is slow (five to ten days), parenteral administration is of no advantage. The plasma half-life is 17 to 36 hours, and this drug is eliminated almost entirely by the kidneys. Lithium clearance averages approximately 20% of creatinine clearance, but significant variability exists among patients.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 313


The population pharmacokinetics of lithium were determined using the nonlinear mixed effects model (NONMEM) program in 79 psychiatric inpatients who were at least 18 yr old, had normal renal function, and were receiving lithium carbonate 2 or 3 times daily. With the initial model, the mean lithium volume of distribution was 32.8 L and the mean lithium clearance was 1.36 L/hr. With an intermediate model, lithium clearance estimates improved on the basis of patient size (weight and body surface area), daily lithium dosage, age, gender, and race. When only the most significant variables, lean body weight and creatinine clearance, were retained, a final model was obtained that yielded a coefficient of variation for lithium clearance of about 24% and gave fairly accurate predictions of steady-state lithium concentrations (coefficient of variation, about 16%). It was concluded that analysis of lithium pharmacokinetics with the nonlinear mixed-effects model program suggested that lean body weight and creatinine clearance are important predictors of lithium clearance.

PMID:2049899 Jermain DE et al; Clin Pharm 10 (May): 376-381 (1991)


Lithium disposition in plasma, red blood cells and urine was studied in acute self-poisoned patient upon chronic lithium therapy (n=4) and in chronic intoxicated patients receiving oral lithium (n=10). Following acute intoxication upon chronic lithium therapy, lithium pharmacokinetics did not differ from previous reports. Terminal plasma half life ranged from 19.0-29.0 hr and RBC/plasma ratio was 0.32 +/- 0.11. the distribution volume of the terminal phase, Vz, was estimated at 0.84 +/- 0.32 L/kg and renal clearance was 0.38 +/- 0.11 ml/mn/kg. After chronic intoxication lithium pharmacokinetics differed from those of the acute patients. Terminal plasma half-life ranged from 36.5-79.4 hr and zero-order decline appeared in 8 of the 10 patients. The RBC/plasma ratio was 0.87 +/- 0.22 on admission. Vz was estimated at 0.71 +/- 0.27 L/kg and renal clearance was 0.16 +/- 0.07 ml/mn/kg. These modifications in lithium elimination kinetics could be related to the decrease in the glomerular filtration rate with age or renal dysfunction in this group of patients.

PMID:7582387 Ferron G et al; Int J Clin Pharmacol Ther 33 (6): 351-5 (1995)


For more Absorption, Distribution and Excretion (Complete) data for LITHIUM CARBONATE (22 total), please visit the HSDB record page.


5.5 Metabolism/Metabolites

Lithium carbonate is not metabolized before excretion.


5.6 Biological Half-Life

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


The plasma half-life is 17 to 36 hours.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 313


The plasma half-life (in healthy volunteers) shows a considerable variability: from 5 to 40 hr, with most values between 15 and 30 hr, it depends on the duration of treatment as well as on kidney function and age. /Li+/

Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 455


The usual elimination half-life is 12 to 27 hr, but it may rise to nearly 60 hr if renal excretion is compromised. /Li+/

Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 852


... The elimination half-life averages 20 to 24 hr. /Li+/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 508


For more Biological Half-Life (Complete) data for LITHIUM CARBONATE (9 total), please visit the HSDB record page.


5.7 Mechanism of Action

Lithium's mechanism of action is still unknown. However, the inositol depletion theory suggests 3 main potential targets. These targets are inositol monophosphatase, inositol polyphosphatase, and glycogen synthase kinase 3(GSK-3). The Inositol depletion theory suggests lithium behaves as an uncompetitive inhibitor of inositol monophosphatase in a manner inversely proportional to the degree of stimulus. This inhibition lowers levels of inositol triphosphate. However, stronger inhibitors of inositol monophosphatase are not as clinically effective and low levels of inositol triphosphate are associated with memory impairment. Lithium acts on inositol polyphosphatase as an uncompetitive inhibitor. This inhibition is thought to have multiple downstream effects that have yet to be clarified. Lithium regulates phosphorylation of GSK-3 which regulates other enzymes through phosphorylation. Lithium can also inhibit GSK-3 through interfering with the magnesium ion in the active site.


Although its antimanic mechanism of action has not been fully determined, lithium is known to affect a variety of neurohumoral signal transduction mechanisms. ... Lithium /lithium carbonate/ counteracts mood changes and is considered the most specific antimanic drug for the prophylaxis and treatment of bipolar disorder.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 311


In animal brain tissue, Li+ at concn of 1 to 10 mEq/L inhibits the depolarization-provoked and Ca+2-dependent release of norepinephrine and dopamine, but not serotonin, from nerve terminals. Li+ may even enhance the release of serotonin, especially in the limbic system, at least transiently. The ion has little effect on catecholamine-sensitive adenylyl cyclase activity or on the binding of ligands to monoamine receptors in brain tissue, although there is some evidence that Li+ can inhibit the effects of receptor-blocking agents that cause supersensitivity in such systems. Li+ can modify some hormonal responses mediated by adenylyl cyclase or phospholipase C in other tissues, including the actions of antidiuretic and thyroid-stimulating hormones on the actions of antidiuretic and thyroid-stimulating hormones on their peripheral target tissues. In part, the actions of Li+ may reflect its ability to interfere with the activity of both stimulatory and inhibitory GTP-binding proteins (Gs and Gi) by keeping them in their less active alpha-beta-gamma trimer state. /Li+/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 508


Lithium inhibits the phosphatase that liberates inositol (I) from inositol phosphate (IP) ... Li+ ... can modify the abundance or function of G proteins and effectors, as well as protein kinases and several cell and nuclear regulatory factors. /Li+, from figure/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 494


Mechanistically, the Li effect results from its substitution for body cations, eg, sodium and potassium, resulting in multisystemic actions. A partial substitution for normal cations causes changes in ion exchange and transfer in cellular processes. Incorporation of Li into membrane structures may alter responses to hormones and the coupling of energy processes ... Among the factors that may modify Li toxicity and kinetics are the type of the poisoning, the presence of the underlying disease, and renal impairment. /Li+/

Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 455


For more Mechanism of Action (Complete) data for LITHIUM CARBONATE (22 total), please visit the HSDB record page.


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