Lithium pharmacology


Lithium pharmacology

Lithium pharmacology refers to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely and in the long term. As a mood stabilizer, lithium is probably more effective in preventing mania than depression, and may reduce the risk of suicide in certain bipolar patients.[1] In depression alone (unipolar disorder) lithium can be used to augment other antidepressants. Lithium carbonate (Li2CO3), sold under several trade names, is the most commonly prescribed, while the citrate salt lithium citrate (Li3C6H5O7) is also used in conventional pharmacological treatments. The sulfate salt lithium sulfate (Li2SO4) has been presented as an alternative[citation needed]. Lithium orotate (orotic acid) is sometimes marketed as a "safe" natural alternative with fewer side-effects than conventional lithium, yet caution must be taken with all of the active lithium salts.

Upon ingestion, lithium becomes widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing norepinephrine release and increasing serotonin synthesis.

Contents

Medical uses

Lithium treatment is used to treat mania in bipolar disorder. Initially, lithium is often used in conjunction with antipsychotic drugs as it can take up to a month for lithium to have an effect. Lithium is also used as prophylaxis for depression and mania in bipolar disorder. It is sometimes used for other psychiatric disorders such as cycloid psychosis and major depressive disorder.[2][3] Lithium possesses a very important antisuicidal effect not shown in other stabilizing medications such as antiseizures drugs.[4][4][5] Non-psychiatric applications are limited; however, its use is well established in the prophylaxis of some headaches related to cluster headaches (trigeminal autonomic cephalgias), particularly hypnic headache. An Italian pilot study in humans conducted in 2005–06 suggested that lithium may improve outcomes in the neurodegenerative disease amyotrophic lateral sclerosis.[6][7] However, a randomised, double-blind, placebo-controlled trial comparing the safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis failed to demonstrate any benefit from a combination therapy over riluzole alone.[8]

Lithium is sometimes used as an augmenting agent to increase the benefits of standard drugs used for unipolar depression. Lithium treatment was previously considered to be unsuitable for children; however, more recent studies show its effectiveness for treatment of early-onset bipolar disorder in children as young as eight. The required dosage (15–20 mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. To prescribe the correct dosage, the patient's entire medical history, both physical and psychological, is sometimes taken into consideration. The starting dosage of lithium should be 400–600 mg given at night and increased weekly depending on serum monitoring.[9]

Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities. As it interferes with the regulation of sodium and water levels in the body, lithium can cause dehydration. Dehydration, which is compounded by heat, can result in increasing lithium levels. The reason why water is lost is because Lithium inhibits the action of antidiuretic hormone (ADH) which enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine leading to consequent loss of body water and thirst.[10]

High doses of haloperidol, fluphenazine, or flupenthixol may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported.

Lithium salts have a narrow therapeutic/toxic ratio and should therefore not be prescribed unless facilities for monitoring plasma concentrations are available. Patients should be carefully selected. Doses are adjusted to achieve plasma concentrations of 0.4[11][12] to 1.2 mmol Li+/L (lower end of the range for maintenance therapy and elderly patients, higher end for pediatric patients) on samples taken 12 hours after the preceding dose. Overdosage, usually with plasma concentrations over 1.5 mmol Li+/L, may be fatal, and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment, confusion, and convulsions. If these potentially hazardous signs occur, treatment should be stopped, plasma lithium concentrations redetermined, and steps taken to reverse lithium toxicity. The most common side effects are an overall dazed feeling and a fine hand tremor. These side effects are generally present during the length of the treatment, but can sometimes disappear in certain patients. Other common side effects, such as nausea and headache, can be generally remedied by a higher intake of water. Lithium unbalances electrolytes; to counteract this, increased water intake is suggested.

Lithium toxicity is compounded by sodium depletion. Concurrent use of diuretics that inhibit the uptake of sodium by the distal tubule (e.g. thiazides) is hazardous and should be avoided. In mild cases, withdrawal of lithium and administration of generous amounts of sodium and fluid will reverse the toxicity. Plasma concentrations in excess of 2.5 mmol Li+/L are usually associated with serious toxicity requiring emergency treatment. When toxic concentrations are reached, there may be a delay of 1 or 2 days before maximum toxicity occurs.

In long-term use, therapeutic concentrations of lithium have been thought to cause histological and functional changes in the kidney. The significance of such changes is not clear, but is of sufficient concern to discourage long-term use of lithium unless it is definitely indicated. Doctors may change a bipolar patient's medication from lithium to another mood stabilizing drug, such as valproate (Depakote), if problems with the kidneys arise. An important potential consequence of long-term lithium usage is the development of renal diabetes insipidus (inability to concentrate urine). Patients should therefore be maintained on lithium treatment after 3–5 years only if, on assessment, benefit persists. Conventional and sustained-release tablets are available. Preparations vary widely in bioavailability, and a change in the formulation used requires the same precautions as initiation of treatment. There are few reasons to prefer any one simple salt of lithium; the carbonate has been the more widely used, but the citrate is also available.

Lithium may be used as a treatment of seborrhoeic dermatitis (Lithium gluconate 8% gel). In addition, lithium has been shown to increase production of white blood cells in the bone marrow and might be indicated in patients suffering from leukopenia.[13]

A limited amount of evidence suggests that lithium may contribute to treatment of substance abuse for some dual-disorder patients.[14][15][16]

Side effects

The average developmental score[clarification needed] for the lithium-exposed group of children was 7–8 points lower than the control group (siblings), but well within the normal range of 100±15.[17] Cognitive depression in adults is disputed.

Lithium is known to be responsible for significant amounts of weight gain.[18] It increases the appetite and thirst ("polydypsia", potentially causing nephrogenic diabetes insipidus), may cause more depression than before with suicidal thoughts and actions, and reduces the activity of thyroid hormone (hypothyroidism).[19][20][21][22][23] It is also believed to affect renal function.[24]

Lithium is a well known cause of downbeat nystagmus.[25] The nystagmus may be permanent or require several months of abstinence for improvement.[26]

Lithium is also a teratogen causing birth defects in a small number of new born babies.[27] If taken during a woman's pregnancy can cause her child to develop Ebstein's anomaly, a heart defect.

Dehydration

Dehydration in patients taking Lithium salts can be very hazardous especially when combined with nephrogenic diabetes insipidus and thus polyuria. Low Natrium in water they drink may very quickly produce hyponatremia with its danger of toxic Lithium concentrations in plasma. Situation such as: preoperative fluid regimen (ECT) or otherwise fluid unaccessibility, warm water conditions, sporting events, hiking.

Overdose

Lithium toxicity may occur in persons taking excessive amounts either accidentally or intentionally on an acute basis or in patients who accumulate high levels during ongoing chronic therapy. The manifestations include nausea, emesis, diarrhea, asthenia, ataxia, confusion, lethargy, polyuria, seizures and coma. Other toxic effects of lithium also include coarse tremor, muscle twitching, convulsions and renal failure.[28] Persons who survive a poisoning episode may develop persistent neurotoxicity.

Measurement in body fluids

Lithium concentrations in whole blood, plasma, serum or urine may be measured using instrumental techniques as a guide to therapy, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Serum lithium concentrations are usually in the 0.5–1.3 mmol/L range in well-controlled patients, but may increase to 1.8–2.5 mmol/L in patients who accumulate the drug over time and to 3–10 mmol/L in victims of acute overdosage.[29][30]

Mechanism of action

Unlike other psychoactive drugs, Li+ typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations.[citation needed]

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. However, because it is a poor substrate at the sodium pump, it cannot maintain a membrane potential and only sustains a small gradient across biological membranes.[citation needed] Li+ is similar enough to Na+ that under experimental conditions, Li+ can replace Na+ for production of a single action potential in neurons.[citation needed]

Recent research suggests three different mechanisms which may or may not act together to deliver the mood-stabilizing effect of this ion.[31] The excitatory neurotransmitter glutamate could be involved in the effect of lithium as other mood stabilizers such as valproate and lamotrigine exert influence over glutamate, suggesting a possible biological explanation for mania.[citation needed] The other mechanisms by which lithium might help to regulate mood include the alteration of gene expression.[32]

An unrelated mechanism of action has been proposed in which lithium deactivates the GSK3β enzyme.[33] This enzyme normally phosphorylates the Rev-Erbα transcription factor protein stabilizing it against degradation. Rev-Erbα in turn represses BMAL1, a component of the circadian clock. Hence lithium by inhibiting GSK3β causes the degradation of Rev-Erbα and increases the expression of BMAL which dampens the circadian clock[34] Through this mechanism, lithium is able to block the resetting of the "master clock" inside the brain; as a result, the body's natural cycle is disrupted. When the cycle is disrupted, the routine schedules of many functions (metabolism, sleep, body temperature) are disturbed. Lithium may thus restore normal brain function after it is disrupted in some people.

Another mechanism proposed in 2007 is that lithium may interact with nitric oxide (NO) signalling pathway in the central nervous system, which plays a crucial role in the neural plasticity. Ghasemi et al. (2008, 2009) have shown that the NO system could be involved in the antidepressant effect of lithium in the Porsolt forced swimming test in mice.[35][36] It was also reported that NMDA receptor blockage augments antidepressant-like effects of lithium in the mouse forced swimming test,[37] indicating the possible involvement of NMDA receptor/NO signaling in the action of lithium in this animal model of learned helplessness.

Lithium treatment has been found to inhibit the enzyme inositol monophosphatase, leading to higher levels of inositol triphosphate.[38] This effect was enhanced further with an inositol triphosphate reuptake inhibitor. Inositol disruptions have been linked to memory impairment and depression.

History

Lithium was first used in the nineteenth century as a treatment for gout after scientists discovered that, at least in the laboratory, lithium could dissolve uric acid crystals isolated from the kidneys. The levels of lithium needed to dissolve urate in the body, however, were toxic.[39] Because of prevalent theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark[40] and William Alexander Hammond in New York[41] used lithium to treat mania from the 1870s onwards though there are reports of its use in the form of spring waters to treat mania in Roman and Greek times. By the turn of the century, this use of lithium was largely abandoned, according to Susan Greenfield due to the reluctance of the pharmaceutical industry to invest in a drug that could not be patented.[42]

As accumulating knowledge indicated a role for excess sodium intake in hypertension and heart disease, lithium salts were prescribed to patients for use as a replacement for dietary table salt (sodium chloride). This practise was discontinued in 1949 when reports of side effects and deaths were published, leading to a ban of lithium sales.[39]

The use of lithium salts to treat mania was rediscovered by the Australian psychiatrist John Cade in 1949. Cade was injecting rodents with urine extracts taken from schizophrenic patients, in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to be psychoactive (adenosine receptors on neurons are stimulated by it; caffeine blocks them), Cade needed soluble urate for a control. He used lithium urate, already known to be the most soluble urate compound, and observed that this caused the rodents to be tranquilized. Cade traced the effect to the lithium ion itself. Soon, Cade proposed lithium salts as tranquilizers, and soon succeeded in controlling mania in chronically hospitalized patients with them. This was one of the first successful applications of a drug to treat mental illness, and it opened the door for the development of medicines for other mental problems in the next decades.[43]

The rest of the world was slow to adopt this treatment, largely because of deaths which resulted from even relatively minor overdosing, including those reported from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmark's Mogens Schou and Paul Baastrup in Europe,[39] and Samuel Gershon and Baron Shopsin in the U.S., this resistance was slowly overcome. The application of lithium for mania in manic illness was approved by the United States Food and Drug Administration in 1970.[44] In 1974 this application was extended to the use of lithium as a preventive agent for manic-depressive illness.

In 2009, Japanese researchers at Oita University reported that low levels of naturally-occurring lithium in drinking water supplies reduced suicide rates.[45] A previous report had found similar data in the American state of Texas.[46] In response, psychiatrist Peter Kramer raised the hypothetical possibility of adding lithium to drinking water.[47]

Lithium has become a part of Western popular culture. Characters in Pi, Premonition, Stardust Memories, American Psycho, and An Unmarried Woman all take lithium. Sirius XM Satellite Radio in North America has a 1990s alternative rock station called Lithium, and several songs refer to the use of lithium as a mood stabilizer. These include: "Lithium Lips" by Mac Lethal, "Equilibrium met Lithium" by South African artist Koos Kombuis, "Lithium" by Evanescence, "Lithium" by Nirvana, "Lithium and a Lover" by Sirenia, "Lithium Sunset", from the album Mercury Falling by Sting,[48] "Tea and Thorazine" by Andrew Bird, and "Lithium" by Thin White Rope.

Use in 7 Up

As with cocaine in Coca-Cola, lithium was widely marketed as one of a number of patent medicine products popular in the late-19th and early-20th centuries, and was the medicinal ingredient of a refreshment beverage, 7 Up. Charles Leiper Grigg, who launched his St. Louis-based company The Howdy Corporation in 1920, invented a formula for a lemon-lime soft drink in 1929. The product, originally named "Bib-Label Lithiated Lemon-Lime Soda", was launched two weeks before the Wall Street Crash of 1929.[49] It contained the mood stabiliser lithium citrate and was one of a number of patent medicine products popular in the late-19th and early-20th centuries.[50] The beverage was marketed specifically as a hangover cure. Its name was soon changed to 7 Up; all American beverage makers were forced to remove lithium in 1948.

References

  1. ^ Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J (2006). "Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.". Bipolar disorders 8 (5 Pt 2): 625–39. doi:10.1111/j.1399-5618.2006.00344.x. PMID 17042835. 
  2. ^ Mash, Eric J.; Russell A. Barkley (2006). Treatment of childhood disorders. Guilford Press. p. 443. ISBN 1572309210. http://books.google.com/?id=KCZqs_NlfmQC. 
  3. ^ Schatzberg, Alan F.; Jonathan O. Cole, Charles DeBattista (2007). Manual of clinical psychopharmacology. American Psychiatric Publishing. p. 267. ISBN 1585623172. http://books.google.com/?id=NvT0l6iL5IQC. 
  4. ^ a b Müller-Oerlinghausen, B; Berghöfer, A; Ahrens, B (2003). "The Antisuicidal and Mortality-Reducing Effect of Lithium Prophylaxis: Consequences for Guidelines in Clinical Psychiatry". Canadian Journal of Psychiatry 48 (7): 433–9. PMID 12971012. https://ww1.cpa-apc.org/Publications/Archives/CJP/2003/august/muller.asp. 
  5. ^ Kovacsics, Colleen E.; Gottesman, Irving I.; Gould, Todd D. (2009). "Lithium's Antisuicidal Efficacy: Elucidation of Neurobiological Targets Using Endophenotype Strategies". Annual Review of Pharmacology and Toxicology 49: 175–198. doi:10.1146/annurev.pharmtox.011008.145557. PMID 18834309. 
  6. ^ "Lithium Slows ALS Progression In Study". Muscular Dystrophy Association. 2008-02-04. http://www.als-mda.org/research/news/080204Lithium_slows_ALS.html. Retrieved 2009-06-23. 
  7. ^ Fornai, F.; Longone, P.; Cafaro, L.; Kastsiuchenka, O.; Ferrucci, M.; Manca, M. L.; Lazzeri, G.; Spalloni, A. et al. (2008). "Lithium delays progression of amyotrophic lateral sclerosis". Proceedings of the National Academy of Sciences 105 (6): 2052–2057. doi:10.1073/pnas.0708022105. 
  8. ^ Aggarwal, SP; Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, Kaufman P, Conwit RA, Schoenfeld D, Shefner J, Cudkowicz M (2010). "Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial". Lancet Neurology 9 (5): 481–8. doi:10.1016/S1474-4422(10)70068-5. PMC 3071495. PMID 20363190. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3071495. 
  9. ^ Semple, David"oxford hand book of psychiatry" oxford press. 2005.
  10. ^ Healy D. 2005. Psychiatric Drugs Explained. 4th ed. Churchhill Livingstone: London.
  11. ^ The UK Electronic Medical Compendium recommends 0.4–0.8 mmol/L plasma lithium level in adlults for Prophylaxis of recurrent affective bipolar manic-depressive illness Camcolit 250 mg Lithium Carbonate Revision 2 December 2010, Retrieved 5 May 2011
  12. ^ One study (Solomon, D.; Ristow, W.; Keller, M.; Kane, J.; Gelenberg, A.; Rosenbaum, J.; Warshaw, M. (1996). "Serum lithium levels and psychosocial function in patients with bipolar I disorder". The American journal of psychiatry 153 (10): 1301–1307. PMID 8831438.  edit) concluded that a "low" dose of 0.4–0.6 mmol/L serum lithium treatment for patients with bipolar 1 disorder had less side effects, but a higher rate of relapse, than a "standard" dose of 0.8–1.0 mmol/L. However, a re-analysis of the same experimental data (Perlis, R.; Sachs, G.; Lafer, B.; Otto, M.; Faraone, S.; Kane, J.; Rosenbaum, J. (2002). "Effect of abrupt change from standard to low serum levels of lithium: A reanalysis of double-blind lithium maintenance data". The American journal of psychiatry 159 (7): 1155–1159. PMID 12091193.  edit) concluded that the higher rate of relapse for the "low" dose was due to abrupt changes in the lithium serum levels
  13. ^ Vieweg, W. V. R.; Yank, Rowe, Hovermale, Clayton (Fall 1986). "Increase in White Blood Cell Count and Serum Sodium Level Following the Addition of Lithium to Carbamazephine Treatment among three chronically Psychotic male Patients with disturbed Affective States". Psychiatric Quarterly 583: 213. http://resources.metapress.com/pdf-preview.axd?code=u11w152782481762&size=largest. Retrieved 2010-04-20. 
  14. ^ Rosenberg, J.; Salzman, C. (2007). "Update: New uses for lithium and anticonvulsants". CNS spectrums 12 (11): 831–841. PMID 17984856.  edit
  15. ^ Frye, M. A.; Salloum, I. M. (2006). "Bipolar disorder and comorbid alcoholism: Prevalence rate and treatment considerations". Bipolar Disorders 8 (6): 677–685. doi:10.1111/j.1399-5618.2006.00370.x. PMID 17156154.  edit
  16. ^ Vornik, L.; Brown, E. (2006). "Management of comorbid bipolar disorder and substance abuse". The Journal of clinical psychiatry 67 Suppl 7: 24–30. PMID 16961421.  edit
  17. ^ Neurobehavioral Outcome following Lithium Exposure
  18. ^ Sperner-Unterweger, Barbara; W. Wolfgang Fleischhacker, Wolfgang P. Kaschka (2001). Psychoneuroimmunology. Karger Publishers. p. 22. ISBN 380557262X. http://books.google.com/?id=Q0xJfkY5VRUC. 
  19. ^ Keshavan, Matcheri S.; John S. Kennedy (2001). Drug-induced dysfunction in psychiatry. Taylor & Francis. p. 305. ISBN 089116961X. http://books.google.com/?id=pol0204fqjIC. 
  20. ^ Side Effects – Lithium / Various Brand Names – Bipolar Disorder Medications
  21. ^ Bipolar Medications and Weight Gain
  22. ^ Nutrition Articles – The Relationship between Weight Gain and Medications for Depression and Seizures
  23. ^ Safer lithium therapy. NHS National Patient Safety Agency. Issue date: 1 December 2009
  24. ^ Bendz, Hans; Schön, Attman, Aurell (February 1, 2010). "Renal failure occurs in chronic lithium treatment but is uncommon". Kidney International 77 (3): 219. doi:10.1038/ki.2009.433. PMID 19940841. 
  25. ^ Lee, Michael S.; Lessell, Simmons (January 28, 2003). "Lithium-induced periodic alternating nystagmus". Neurology (journal) 60 (2): 344. doi:10.1212/01.WNL.0000042787.51461.D1. PMID 12552061. 
  26. ^ Williams, Douglas P.; Jack Rogers and B. Todd Troost (September 1988). "Lithium-Induced Downbeat Nystagmus". Archives of Neurology 45 (9): 1022–1023. doi:10.1212/01.WNL.0000042787.51461.D1. PMID 12552061. 
  27. ^ Shepard, TH.; Brent, RL.; Friedman, JM.; Jones, KL.; Miller, RK.; Moore, CA.; Polifka, JE. (2002). "Update on new developments in the study of human teratogens". Teratology 65 (4): 153–61. doi:10.1002/tera.10032. PMID 11948561. 
  28. ^ Gelder, M., Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp249.
  29. ^ Amdisen A. (1978). "Clinical and serum level monitoring in lithium therapy and lithium intoxication". J. Anal. Toxicol. 2: 193–202. 
  30. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 851–854.
  31. ^ Jope RS (1999). "Anti-bipolar therapy: mechanism of action of lithium". Mol. Psychiatry 4 (2): 117–128. doi:10.1038/sj.mp.4000494. PMID 10208444. 
  32. ^ Lenox RH, Wang L (February 2003). "Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks". Mol. Psychiatry 8 (2): 135–44. doi:10.1038/sj.mp.4001306. PMID 12610644. 
  33. ^ Klein PS, Melton DA (August 1996). "A molecular mechanism for the effect of lithium on development". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8455–9. doi:10.1073/pnas.93.16.8455. PMC 38692. PMID 8710892. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38692. 
  34. ^ Yin L, Wang J, Klein PS, Lazar MA (February 2006). "Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock". Science 311 (5763): 1002–5. doi:10.1126/science.1121613. PMID 16484495. Lay summary – The Scientist. 
  35. ^ Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR (May 2008). "Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test". Eur Neuropsychopharmacol 18 (5): 323–32. doi:10.1016/j.euroneuro.2007.07.011. PMID 17728109. 
  36. ^ Ghasemi M, Sadeghipour H, Poorheidari G, Dehpour AR (June 2009). "A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test". Behav. Brain Res. 200 (1): 76–82. doi:10.1016/j.bbr.2008.12.032. PMID 19166880. 
  37. ^ Ghasemi M, Raza M, Dehpour AR (April 2010). "NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test". J. Psychopharmacol. (Oxford) 24 (4): 585–94. doi:10.1177/0269881109104845. PMID 19351802. 
  38. ^ Einat H, Kofman O, Itkin O, Lewitan RJ, Belmaker RH (1998). "Augmentation of lithium's behavioral effect by inositol uptake inhibitors". J Neural Transm 105 (1): 31–8. doi:10.1007/s007020050035. PMID 9588758. 
  39. ^ a b c Marmol, F. (2008). "Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium". Progress in neuro-psychopharmacology & biological psychiatry 32 (8): 1761–1771. doi:10.1016/j.pnpbp.2008.08.012. PMID 18789369.  edit
  40. ^ Lenox, RH; Watson, DG (1994). "Lithium and the brain: a psychopharmacological strategy to a molecular basis for manic depressive illness". Clinical chemistry 40 (2): 309–14. PMID 8313612. 
  41. ^ Mitchell, PB; Hadzi-Pavlovic, D (2000). "Lithium treatment for bipolar disorder". Bulletin of the World Health Organization 78 (4): 515–7. PMC 2560742. PMID 10885179. https://www.who.int/entity/bulletin/archives/78(4)515.pdf. 
  42. ^ Greenfield, Susan: "Brain Power: Working out the Human Mind", page 91. Element Books Limited, 1999
  43. ^ Cade J. F. J. (1949). "Lithium salts in the treatment of psychotic excitement" (PDF). Medical Journal of Australia 2 (10dfbnm): 349–52. PMID 18142718. http://www.who.int/docstore/bulletin/pdf/2000/issue4/classics.pdf. 
  44. ^ P. B. Mitchell, D. Hadzi-Pavlovic (2000). "Lithium treatment for bipolar disorder" (PDF). Bulletin of the World Health Organization 78 (4): 515–7. PMC 2560742. PMID 10885179. http://www.who.int/docstore/bulletin/pdf/2000/issue4/classics.pdf. 
  45. ^ Ohgami H. Terao T. et al, Lithium levels in drinking water and risk of suicide. British Journal of Psychiatry. 194(5):464–5; discussion 446, May 2009
  46. ^ Gonzalez R. Bernstein I., et al. An investigation of water lithium concentrations and rates of violent acts in 11 Texas counties: can an association be easily shown? Journal of Clinical Psychiatry. 69(2):325–6, 2008 Feb.
  47. ^ Listening to Lithium Sept 9. 2009
  48. ^ Agassi, Tirzah (1996-03-12). "Sting is now older, wiser and duller". The Jerusalem Post. http://pqasb.pqarchiver.com/jpost/access/62551750.html?dids=62551750:62551750&FMT=ABS&FMTS=ABS:FT&date=Mar+12%2C+1996&author=TIRZAH+AGASSI&pub=Jerusalem+Post&desc=Sting+is+now+older%2C+wiser+and+duller. Retrieved 2009-06-25. 
  49. ^ "7 UP: The Making of a Legend". Cadbury Schweppes: America's Beverages.
  50. ^ "Urban Legends Reference Pages: 7Up". http://www.snopes.com/business/names/7up.asp. Retrieved 2007-11-13. 

External links


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Lithium carbonate — IUPAC name Lithium carbonate …   Wikipedia

  • Lithium (disambiguation) — Lithium is a chemical element. It may also refer to: In science *Lithium ion battery, a battery used in electronics *Lithium pharmacology, mood stabilizing drugs In music * Lithium (Nirvana song), a single from Nirvana s second album Nevermind *… …   Wikipedia

  • Lithium chloride — Chembox new Name = Lithium chloride ImageFile1 = Lithium chloride.jpg ImageSize1 = 150px ImageName1 = Lithium chloride ImageFile2 = Lithium chloride 3D ionic.png ImageSize2 = 150px ImageName2 = Lithium chloride IUPACName = Lithium Chloride… …   Wikipedia

  • Lithium citrate — chembox Name = Lithium citrate ImageFile = Lithium citrate 2D skeletal.png ImageSize = 225px ImageName = Lithium citrate OtherNames = Trilithium citrate trilithium 2 hydroxypropane 1,2,3 tricarboxylate Section1 = Chembox Identifiers CASNo = 919… …   Wikipedia

  • Lithium sulfate — Chembox new Name = Lithium sulfate ImageFile = Lithium sulfate.jpg ImageName = Lithium sulfate IUPACName = Lithium sulfate OtherNames = Lithium sulphate Section1 = Chembox Identifiers SMILES = CASNo = 10377 48 7 RTECS = Section2 = Chembox… …   Wikipedia

  • Lithium — Eigenschaften …   Deutsch Wikipedia

  • lithium — /lith ee euhm/, n. 1. Chem. a soft, silver white metallic element, the lightest of all metals, occurring combined in certain minerals. Symbol: Li; at. wt.: 6.939; at. no.: 3; sp. gr.: 0.53 at 20°C. 2. Pharm. the substance in its carbonate or… …   Universalium

  • Gabapentin — Systematic (IUPAC) name 2 [1 (aminomethyl)cyclohexyl]acetic acid …   Wikipedia

  • Oxcarbazepine — Systematic (IUPAC) name 10,11 dihydro 10 …   Wikipedia

  • Carbamazepine — Systematic (IUPAC) name 5 …   Wikipedia