PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
lithium

2D structure

Overview

Trade Names: Eskalith; LithoTab
PharmGKB Accession Id: PA450243

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. (source: Drug Bank)

ATC Therapeutic Categories

  • D11AX:Other dermatologicals
  • N05AN:Lithium

Pharmacology, Interactions, and Contraindications

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. (source: Drug Bank)

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. (source: Drug Bank)

Isomeric SMILES Code:

[Li+] (source: PharmGKB)

Curated Annotations (Curated Annotation)

  1. rs2284017 at chr22:35426873 in CACNG2
    The C allele of this variant is associated with increased response of patients with bipolar disorder to lithium treatment relative to that observed in patients carrying two copies of the T allele. This association was observed in two separate cohorts: one of 188 patients, and one of 151 patients.
    Related Drugs:
    lithium
    Related Diseases:
    Bipolar Disorder
    Evidence:
    PMID:18408563
  2. rs2284018 at chr22:35427510 in CACNG2
    The C allele of this variant is associated with increased response of patients with bipolar disorder to lithium treatment relative to that observed in patients carrying two copies of the T allele. This association was seen in one cohort of 161 patients, but not in a separate cohort of 197 patients.
    Related Drugs:
    lithium
    Related Diseases:
    Bipolar Disorder
    Evidence:
    PMID:18408563
  3. rs5750285 at chr22:35434194 in CACNG2
    The C allele of this variant is associated with increased response of patients with bipolar disorder to lithium treatment relative to that observed in patients carrying two copies of the G allele. This association was seen in one cohort of 195 patients, but not in a separate cohort of 134 patients.
    Related Drugs:
    lithium
    Related Diseases:
    Bipolar Disorder
    Evidence:
    PMID:18408563
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
BDNF
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
CACNG2
  •   
  •   
  •   
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
CREB1
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
GSK3B
  •   
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
IMPA2
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
INPP1
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
KCNQ2
  •   
  •   
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
MAPT
  • CO
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
NR1D1
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
NTRK2
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PPP2R2C
  •   
  •   
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
XBP1
  •   
  •   
  •   
  •   
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
CTNNB1 Uncurated Annotation (source: Drug Bank)
GSK3B Uncurated Annotation (source: Drug Bank)
INPP1 Uncurated Annotation (source: Drug Bank)
IMPA1 Uncurated Annotation (source: Drug Bank)
IMPA2 Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
benazepril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
bendroflumethiazide Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
bromfenac Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
caffeine Uncurated Annotation Caffeine decreases serum levels of lithium (source: Drug Bank)
candesartan Uncurated Annotation The ARB increases serum levels of lithium (source: Drug Bank)
captopril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
celecoxib Uncurated Annotation The COX-2 inhibitor increases serum levels of lithium (source: Drug Bank)
chlorothiazide Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
chlorthalidone Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
citric acid Uncurated Annotation The urine alkalizer decreases the effect of lithium (source: Drug Bank)
cyclothiazide Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
diclofenac Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
enalapril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
eprosartan Uncurated Annotation The ARB increases serum levels of lithium (source: Drug Bank)
fluoxetine Uncurated Annotation The SSRI increases serum levels of lithium (source: Drug Bank)
fluvoxamine Uncurated Annotation The SSRI increases serum levels of lithium (source: Drug Bank)
fosinopril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
haloperidol Uncurated Annotation Possible extrapyramidal effects and neurotoxicity with this combination (source: Drug Bank)
hydrochlorothiazide Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
ibuprofen Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
indapamide Uncurated Annotation The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
indomethacin Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
iodine Uncurated Annotation Possible hypothyroidism with this combination (source: Drug Bank)
irbesartan Uncurated Annotation The ARB increases serum levels of lithium (source: Drug Bank)
ketorolac Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
l-methyldopa Uncurated Annotation Signs of increased lithium without increase with this combination (source: Drug Bank)
lisinopril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
losartan Uncurated Annotation Losartan increases serum levels of lithium (source: Drug Bank)
mefenamic acid Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
meloxicam Uncurated Annotation Meloxicam increases serum levels of lithium (source: Drug Bank)
metronidazole Uncurated Annotation Metronidazole increases the effect and toxicity of lithium (source: Drug Bank)
naproxen Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
perindopril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
phenylbutazone Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
piroxicam Uncurated Annotation The NSAID increases serum levels of lithium (source: Drug Bank)
potassium Uncurated Annotation The urine alkalizer decreases the effect of lithium (source: Drug Bank)
quinapril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
ramipril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
rofecoxib Uncurated Annotation The COX-2 inhibitor increases serum levels of lithium (source: Drug Bank)
sibutramine Uncurated Annotation Possible serotoninergic syndrome with this combination (source: Drug Bank)
sodium bicarbonate Uncurated Annotation The urine alkalizer decreases the effect of lithium (source: Drug Bank)
sumatriptan Uncurated Annotation Possible serotoninergic syndrome with this combination (source: Drug Bank)
telmisartan Uncurated Annotation The ARB increases serum levels of lithium (source: Drug Bank)
theophylline Uncurated Annotation Theophylline decreases serum levels of lithium (source: Drug Bank)
topiramate Uncurated Annotation Topiramate could modify lithium levels (source: Drug Bank)
trandolapril Uncurated Annotation The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
valdecoxib Uncurated Annotation The COX-2 inhibitor increases serum levels of lithium (source: Drug Bank)
valsartan Uncurated Annotation The ARB increases serum levels of lithium (source: Drug Bank)
verapamil Uncurated Annotation Signs of lithium toxicity (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alzheimer Disease
  • CO
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Bipolar Disorder
  • CO
  • PD
  •   
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Schizophrenia
  •   
  •   
  •   
  • FA
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Drug-Induced Long QT Intervals
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Dan Roden, MD involving ADRB1, ADRB2, KCNE1, KCNE2, KCNH2, KCNQ1, SCN5A, almokalant, amiodarone, amitriptyline, bretylium, bupivacaine, cisapride, disopyramide, dofetilide, encainide, fluconazole, haloperidol, hydroquinidine, isoflurane, itraconazole, ketoconazole, lithium, loratadine, metoclopramide, nortriptyline, procainamide, quinidine, sematilide, sotalol, sulfamethoxazole, thioridazine, trimethoprim, , Long QT Syndrome, Proarrhythmia and Torsades de Pointes

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01356
ChEBI ID:
30142
KEGG Compound ID:
C15473
PubChem Compound ID:
28486
PubChem Substance ID:
11538471

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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