[1]. Mitra Assadi, et al. Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease. Eur J Paediatr Neurol. 2010 Jul;14(4):354-9.

Lithium citrate may cause developmental toxicity depending on state or federal labeling requirements. Anhydrous lithium citrate is a lithium salt, the anhydrous form of trilithium citrate. The tetrahydrate form is used as a lithium source to treat anxiety, bipolar disorder, and depression. It contains citrate (3-). Lithium citrate is the citrate salt of lithium, a monovalent cation with antimanic activity. While the exact mechanism is unclear, lithium may exert its mood-stabilizing effect by reducing catecholamine concentrations, which is mediated by sodium-potassium-stimulated adenosine triphosphatase (Na-K-ATPase)-mediated transneuronal sodium ion transport. Alternatively, lithium may reduce cyclic adenosine monophosphate (cAMP) concentrations, thereby desensitizing hormone-sensitive adenylate cyclase receptors. Furthermore, lithium at recommended doses inhibits the activity of inositol-1-phosphatase, leading to decreased levels of the postsynaptic second messengers diacylglycerol and inositol triphosphate, which promote chronic cellular stimulation by altering neuronal electrical activity. See also: Lithium ions (with active portion).

---

Drug Indications
Lithium is used as a mood stabilizer to treat depression and mania. It is commonly used to treat bipolar disorder.

---

Mechanism of Action
Currently, the exact mechanism of action of lithium ions as a mood stabilizer is unclear. Lithium ions may exert their effects through interactions with the transport of monovalent or divalent cations in neurons. A growing number of scientists believe that the excitatory neurotransmitter glutamate is a key factor in understanding the mechanism of lithium action. Lithium has been shown to alter the inward and outward currents of glutamate receptors, particularly GluR3, without changing their inversion potential. Studies have found that lithium has a dual effect on glutamate receptors, maintaining a stable and healthy concentration of active glutamate in the intercellular space—neither too much nor too little. Some studies speculate that excessive glutamate in the interneuronal space leads to mania, while insufficient glutamate leads to depression. Another mechanism by which lithium regulates mood may be through non-competitive inhibition of an enzyme called inositol monophosphatase. Furthermore, the effects of lithium may also be enhanced by inhibiting the activity of the GSK-3B enzyme. Lithium regulation of GSK-3B may affect the biological clock. GSK-3 is known for phosphorylating and inactivating glycogen synthase. GSK-3B is also involved in regulating cellular responses to DNA damage. GSK-3 normally phosphorylates β-catenin, leading to β-catenin degradation. When GSK-3 is inhibited, β-catenin levels increase, and transgenic mice overexpressing β-catenin exhibit behavior similar to lithium-treated mice. These results suggest that elevated β-catenin levels may be one pathway by which lithium exerts its therapeutic effects.

---

Pharmacodynamics
Although lithium has been used to treat bipolar disorder for over 50 years, its mechanism of action remains unclear. The therapeutic effects of lithium may stem from a variety of effects, including inhibition of enzymes such as glycogen synthase kinase 3 and inositol phosphatase, or regulation of glutamate receptors.

C6H5LI3O7

209.92

210.052

919-16-4

Lithium citrate tetrahydrate;6080-58-6

13520

Typically exists as solid at room temperature

1.12 g/mL at 20 °C

309.6ºC at 760mmHg

155.2ºC

1

7

2

16

211

0

[Li].O=C(CC(CC(O)=O)(C(O)=O)O)O

WJSIUCDMWSDDCE-UHFFFAOYSA-K

InChI=1S/C6H8O7.3Li/c7-3(8)1-6(13,5(11)12)2-4(9)10;;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;;/q;3*+1/p-3

trilithium;2-hydroxypropane-1,2,3-tricarboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)