17341-24-1 Usage
Mechanism of action
Lithium therapy for disorders is believed to be effective because of its ability to reduce signal transduction
through the phosphatidylinositol signaling pathway. In this pathway, the second
messengers diacylglycerol and inositol 1,4,5-trisphosphate are produced from the enzymatic hydrolysis of
phosphatidylinositol-4,5-bisphosphate (a membrane phospholipid) by the receptor-mediated activation of the
membrane-bound, phosphatidylinositol-specific phospholipase C. The second messenger activity for inositol
1,4,5-trisphosphate is terminated by its hydrolysis in three steps by inositol monophosphatases to inactive
inositol, thus completing the signaling pathway. To recharge the signaling pathway, inositol must be recycled
back to phosphatidylinositol bisphosphate by inositol phospholipid–synthesizing enzymes in the CNS,
because inositol is unable to cross the blood-brain barrier into the CNS in sufficient concentrations to
maintain the signaling pathway. By uncompetitive inhibition of inositol phosphatases in the signaling pathway,
the therapeutic plasma concentrations of lithium ion deplete the pool of inositol available for the resynthesis
of phosphatidylinositol-4,5- bisphosphate, ultimately decreasing its cellular levels and, thereby,reducing the enzymatic formation of the second messengers. Thus, lithium ion restores the balance among
aberrant signaling pathways in critical regions of the brain.
The effects of lithium ion on disorders are surprisingly specific because of the inability of inositol to cross the
blood-brain barrier and replenish depleted inositol levels. Lithium ion exerts its greatest influence on this
signaling pathway when the lithium ion concentration is at saturation conditions.
The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is
characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term
therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and GSK-3
signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and
have been implicated in modulating synaptic function in nerve terminals.
Pharmacokinetics
The absorption of lithium is rapid and complete within 6 to 8 hours. The absorption rate of slow-release
capsules is slower and the total amount of lithium absorbed lower than with other dosage forms. Lithium is not
protein bound. The elimination half-life for elderly patients (39 hours) is longer than that for adult patients (24
hours), which in turn is longer than that for adolescent patients (18 hours). The time to peak serum
concentration for lithium carbonate is dependent on the dosage form (tablets, 1–3 hours; extended tab, 4
hours; slow release, 3 hours). Steady-state serum concentrations are reached in 4 days, with the desirable
dose targeted to give a maintenance lithium ion plasma concentration range of 0.6 to 1.2 mEq/L, with a level of 0.5 mEq/L for elderly patients. The risk of bipolar recurrence was approximately threefold greater for
patients with lithium dosages that gave plasma concentrations of 0.4 to 0.6 mEq/L. Adverse reactions are
frequent at therapeutic doses, and adherence is a big problem. Toxic reactions are rare at serum lithium ion
levels of less than 1.5 mEq/L. Mild to moderate toxic reactions may occur at levels from 1.5 to 2.5 mEq/L, and
severe reactions may be seen at levels from 2.0 to 2.5 mEq/L, depending on individual response. The onset
of therapeutic action for clinical improvement is 1 to 3 weeks. Renal elimination of lithium ion is 95%, with
80% actively reabsorbed in the proximal tubule. The rate of lithium ion urinary excretion decreases with age.
Fecal elimination is less than 1%.
Clinical Use
For many years, lithium has been the treatment of choice for bipolar disorder, because it can be effective in
smoothing out the mood swings common to this condition. Its use must be carefully monitored, however,
because the range between an effective and a toxic dose is small.Lithium carbonate (Eskalith) is the most commonly used salt of lithium to treat manic depression. Lithium
carbonate dosage forms are labeled in mg and mEq/dosage unit, and lithium citrate (Lithobid) is labeled as
mg equivalent to lithium carbonate and mEq/dosage unit. Lithium is effectively used to control and prevent
manic episodes in 70 to 80% of those with bipolar disorder as well as to treat other forms of depression.
Those who respond to lithium for depression often are those who have not responded to TCAs after several
weeks of treatment. When giving lithium in addition to their antidepressants, some of these people have
shown significant improvement.
Side effects
Common side effects of lithium include nausea, loss of appetite, and mild diarrhea, which usually taper off
within first few weeks. Dizziness and hand tremors also have been reported. Increased production of urine
and excessive thirst are two common side effects that usually are not serious problems, but patients with
kidney disease should not be given lithium. Taking the day's dosage of lithium at bedtime also seems to help
with the problem of increased urination. Other side effects of lithium include weight gain, hypothyroidism,
increased white blood cell count, skin rashes, and birth defects.
While on lithium, a patient's blood level must be closely monitored. If the blood level of lithium ion is too low,
the patient's symptoms will not be relieved. If the blood level of lithium ion is too high, there is a danger of a
toxic reaction.
Drug interactions
Lithium pharmacokinetics may be influenced by a number of factors, including age. Elderly patients require
lower doses of lithium to achieve serum concentrations similar to those observed in younger adults as a result
of reduced volume of distribution and reduced renal clearance. Lithium ion clearance decreases as the glomerular filtration rate decreases with
increasing age. Reduced lithium ion clearance is expected in patients with hypertension, congestive heart
failure, or renal dysfunction. Larger lithium ion maintenance doses are required in obese compared with
nonobese patients. The most clinically significant pharmacokinetic drug interactions associated with lithium
involve drugs that are commonly used in the elderly and that can increase serum Li+
concentrations. People
who are taking lithium should consult their physician before taking the following drugs: acetazolamide,
antihypertensives, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, calcium
channel blockers, carbamazepine, thiazide diuretics, hydroxyzine, muscle relaxants, neuroleptics, table salt,
baking powder, tetracycline, TCAs, MAOIs, and caffeine. The tolerability of lithium is lower in elderly patients.
Lithium toxicity can occur in the elderly at concentrations considered to be “therapeutic” in the general adult
populations. Serum concentrations of lithium ion need to be markedly reduced in the elderly population—and
particularly so in the very old and frail.
Check Digit Verification of cas no
The CAS Registry Mumber 17341-24-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,7,3,4 and 1 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 17341-24:
(7*1)+(6*7)+(5*3)+(4*4)+(3*1)+(2*2)+(1*4)=91
91 % 10 = 1
So 17341-24-1 is a valid CAS Registry Number.
InChI:InChI=1/Li/q+1
17341-24-1Relevant articles and documents
Relaxation Kinetics and Infrared Spectra of the Complexation of Lithium Ion by Triethylene Glycol and by Tetraethylene Glycol in Acetonitrile
Cobranchi, Daryl P.,Garland, Ben A.,Masiker, Marilyn C.,Eyring, Edward M.,Firman, Paul,Petrucci, Sergio
, p. 5856 - 5865 (1992)
Ultrasonic absorption relaxation spectra are reported covering the frequency range ca. 1-500 MHz for the complexation of LiClO4 by the open-chain polyethers triethylene glycol (EG3) and tetraethylene glycol (EG4) in acetonitrile at 25 deg C and at a molar ratio R = / or R = / = 1.The ultrasonic spectra can be described by the sum of two Debye relaxation processes which were interpreted according to the Eigen-Winkler mechanism Li+ + EG Li+...EG Li+EG (Li+EG) (where EG denotes either EG3 or EG4), giving the rateconstants k1, k-1, k2, and k-2.The first step is taken to be a preequilibrium step for which K0 is calculated from classical statistical theory.The rate constants are compared with those of the corresponding process involving triglyme and poly(ethylene oxide) (PEO) previously reported.Infrared data for the 3800-3200-cm-1 region show a shift of 70 cm-1 to lower energy, indicating a strong interaction between the ethanolic oxygen of EG3 and the Li+ ion.
Latimer, W. M.,Schutz, P. W.,Hicks, J. F. G.
, p. 82 - 84 (1934)
Li12Si7, a Compound with Trigonal Planar Si4 Clusters and Isometric Si5 Rings
Nesper, Reinhard,Schnering, Hans Georg von,Curda, Jan
, p. 3576 - 3590 (2007/10/02)
Li12Si7 is the silicon richest compound of the binary system Li/Si, which does not contain a MX phase contrary to the other I-IV systems.Li12Si7 is formed by direct synthesis from the elements.The compound reacts like an alkali metal forming silanes under hydrolysis and amorphous silicon in the reaction with benzophenone (THF), respectively.The metallic grey phase grows in form of orthorhombic rod-shaped crystals (a = 860.0, b = 1975.5, c = 1433.5 pm at 290 K; Pnma, Z = 8).The crystal structure (at 290 K, R = 0.04, and at 140 K, R = 0.02) exhibits two novel Sin clusters, namely a trigonal planar Si4 star and a planar cyclopentadienyl-like Si5 ring (Si-Si = 237.8 and 236.8 pm, resp.) which are enveloped by Li atoms (Li-Si = 259-309 pm).Li12Si7 is a diamagnetic semiconductor (Eg = 0.6 eV), which however does not fulfil in a simple way the classical electron counting rules for Zintl phases.The complicated 3D structure can be separated into two well chosen one dimensional partial structures Li12Si4 and Li6Si5, which allow for a quantum mechanical treatment.The resulting electronic structure gives rise to a reasonable improvement of the Zintl rules for elements of the higher periods.Li6Si5 = Li5(LiSi5) (26e) is in fact an infinite 1D sandwich stack, a lithiosilacen.In the Li12Si4 fragment (28e) a cage orbital occurs, which has amplitudes at all lithium sites.The stabilisation of the CO32- like geometry and the silicon backbone is mainly due this additional state.