Препараты лития в психиатрии, наркологии и неврологии. Часть II. Биохимическая

Литий – первый и самый лёгкий в ряду щелочных металлов, к которому принадлежат, помимо лития, весьма биологически важные макроэлементы – натрий и калий, а также микроэлементы рубидий и цезий. Несмотря на свою формальную принадлежность к группе щелочных металлов, литий, как и многие другие химические элементы «атипичного» второго периода таблицы Менделеева (например, бор), по ряду своих химических свойств больше похож не на своих собратьев по группе, а на своего «диагонального собрата» – на магний. Как мы покажем в данной статье, диагональное сходство лития с магнием имеет большое значение для понимания механизмов его внутриклеточного биохимического действия. В то же время внутригрупповое химическое сходство лития с натрием и калием имеет большее значение для понимания механизмов его всасывания, распределения в организме и выведения. Несмотря на 70 лет, прошедшие со дня переоткрытия Джоном Кейдом антиманиакального эффекта лития, механизмы его терапевтического действия до сих пор остаются не до конца понятными. Известно, что в механизмах действия лития играет роль его влияние на целый ряд важных внутриклеточных ферментов, таких, как инозитол-монофосфатаза, гормон-чувствительная аденилатциклаза, фосфоаденозин-фосфатаза, протеинкиназа C и другие, и на целый ряд внутриклеточных сигнальных каскадов, таких, как ретиноидный, каннабиноидный, моноаминергические и другие. В конечном итоге оказывается, что механизм терапевтического действия лития чрезвычайно сложный, многокомпонентный, уникальный и неповторимый. Отдельные аспекты механизма его действия могут совпадать с механизмами действия других нормотимиков, или же с механизмами действия экспериментальных так называемых «литий-миметиков», таких, как эбселен. Однако во всей полноте воспроизвести биохимическое действие лития на организм ни одним другим «литий-миметиком» пока не удалось.

1. Birch NJ. (Ed.). Lithium and the cell: pharmacology and biochemistry. New York: Academic Press; 2012.

2. Williams RB, Harwood AJ. Lithium metallotherapeutics. In: Gielen M, Tiekink ERT. (eds.) Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine. New York: John Wiley and Sons; 2005. 1-18.

3. Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical applications.Cambridge: Cambridge University Press; 2013.

4. Goodman LS. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill; 1996.

5. Ruiz P. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. Cambridge: Cambridge University Press; 2017.

6. Kline NS. The history of lithium usage in psychiatry.[Lecture] Boston; 1968.

7. Barr RD, Clarke WB, Clarke RM, Venturelli J, Norman GR, Downing RG. Regulation of lithium and boron levels in normal human blood: environmental and genetic considerations. J Lab Clin Med. 1993; 121(4): 614-619.

8. Clarke WB, Clarke RM, Olson EK, Barr RD, Downing RG. Binding of lithium and boron to human plasma proteins. Biol Trace Elem Res. 1998; 65(3): 237-249. doi: 10.1007/BF02789099

9. Clarke WB, Guscott R, Downing RG, Lindstrom RM. Endogenous lithium and boron red cell-plasma ratios. Biol Trace Elem Res. 2004; 97(2): 105-115. doi: 10.1385/BTER:97:2:105

10. Huang X, Lei Z, El-Mallakh RS. Lithium normalizes elevated intracellular sodium. Bipolar Disord. 2007; 9(3): 298-300. doi: 10.1111/j.1399-5618.2007.00429.x

11. Walz W, Hertz E, Hertz L. Lithium-potassium interaction in acutely treated cortical neurons and astrocytes. Prog Neuropsychopharmacol Biol Psychiatry. 1983; 7(4-6): 697-702.

12. Carr SJ, Thomas TH, Wilkinson R. Erythrocyte sodium-lithium countertransport in primary and renal hypertension: relation to family history. Eur J Clin Invest. 1989; 19(1): 101-106. doi: 10.1111/j.1365-2362.1989.tb00203.x

13. El-Mallakh RS, Barrett JL, Jed Wyatt R. The Na, K-ATPase Hypothesis for Bipolar Disorder: Implications of Normal Development. J Child Adolesc Psychopharmacol. 1993; 3(1): 37-52. doi: 10.1089/cap.1993.3.37

14. Zheng X, Morrison AC, Turner ST, Ferrell RE. Association between SLC20A1 and sodium-lithium countertransport. Am J Hypertens. 2011; 24(10): 1069-1072. doi: 10.1038/ajh.2011.130

15. Wissocq JC, Attias J, Thellier M. Exotic effects of lithium. In: Birch N. (ed.) Lithium and the Cell. New York: Academic Press; 1991. 7-34.

16. Anke MK, Angelov L. Rubidium. In: Merian E, Anke M, Ihnat M, Stoeppler M (Eds.). Elements and their compounds in the environment: Occurrence, analysis and biological relevance. 2nd ed. Weinheim: Wiley-VCH Verlag GmbH; 2004. 547-563.

17. Nielsen FH. Knowledge and speculation. Biol Trace Elem Res. 1998; 11: 251-274.

18. Jakobsson E, Argüello-Miranda O, Chiu SW, Fazal Z, Kruczek J, Nunez-Corrales S, Pandit S, Pritchet L. Towards a Unified Understanding of Lithium Action in Basic Biology and its Significance for Applied Biology. J Membr Biol. 2017; 250(6): 587-604. doi: 10.1007/s00232-017-9998-2

19. Malhi GS, Tanious M, Das P, Coulston CM, Berk M. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS drugs. 2013; 27(2): 135-153. doi: 10.1007/s40263-013-0039-0

20. Dubovsky SL, Daurignac E, Leonard KE. Increased platelet intracellular calcium ion concentration is specific to bipolar disorder. J Affect Disord. 2014; 164: 38-42. doi: 10.1016/j.jad.2014.04.025

21. Uemura T, Green M, Warsh JJ. CACNA1C SNP rs1006737 associates with bipolar I disorder independent of the Bcl-2 SNP rs956572 variant and its associated effect on intracellular calcium homeostasis. World J Biol Psychiatry. 2016; 17(7): 525-534. doi: 10.3109/15622975.2015.1019360

22. Rice AM, Li J, Sartorelli AC. Combination of all-trans retinoic acid and lithium chloride surmounts a retinoid differentiation block induced by expression of Scl and Rbtn2 transcription factors in myeloid leukemia cells. Leuk Res. 2004; 28(4): 399-403. doi: 10.1016/j.leukres.2003.08.011

23. Misiuta IE, Saporta S, Sanberg PR, Zigova T, Willing AE. Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells. J Neurosci Res. 2006; 83(4): 668-679. doi: 10.1002/jnr.20718

24. Rico-Sergado L, Pérez-Canales JL, Pérez-Santonja JJ, Cigüenza-Sancho S. Severe keratomalacia after 12 months of continuous hydrogel contact lens wear in a psychiatric patient. Cont Lens Anterior Eye. 2015; 38(2): 138-141. doi: 10.1016/j.clae.2014.10.005

25. Nikoui V, Javadi-Paydar M, Salehi M, Behestani S, Dehpour AR. Protective Effects of Lithium on Sumatriptan-Induced Memory Impairment in Mice. Acta Med Iran. 2016; 54(4): 226-232.

26. Massot O, Rousselle JC, Fillion MP, Januel D, Plantefol M, Fillion G. 5-HT1B receptors: a novel target for lithium: possible involvement in mood disorders. Neuropsychopharmacology. 1999; 21(4): 530-541. doi: 10.1016/S0893-133X(99)00042-1

27. Scheuch K, Höltje M, Budde H, Lautenschlager M, Heinz A, Ahnert-Hilger G, Priller J. Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons. Brain Res. 2010; 1307: 14-21. doi: 10.1016/j.brainres.2009.10.027

28. Rahimi HR, Dehpour AR, Mehr SE, Sharifzadeh M, Ghahremani MH, Razmi A, Ostad SN. Lithium attenuates cannabinoid-induced dependence in the animal model: involvement of phosphorylated ERK1/2 and GSK-3β signaling pathways. Acta Med Iran. 2014; 52(9): 656-663.

29. Rahimi HR, Ghahremani MH, Dehpour AR, Sharifzadeh M, Ejtemaei-Mehr S, Razmi A, Ostad SN. The Neuroprotective effect of lithium in cannabinoid dependence is mediated through modulation of cyclic AMP, ERK1/2 and GSK-3β phosphorylation in cerebellar granular neurons of rat. Iran J Pharm Res. 2015; 14(4): 1123-1135.

30. Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J Neurosci. 2001; 21(24): 9867-9876. doi: 10.1523/JNEUROSCI.21-24-09867.2001

31. Johnston J, Lintzeris N, Allsop DJ, Suraev A, Booth J, Carson DS, Helliwell D, Winstock A, McGregor IS. Lithium carbonate in the management of cannabis withdrawal: a randomized placebo-controlled trial in an inpatient setting. J Psychopharm. 2014; 231(24): 4623-4636. doi: 10.1007/s00213-014-3611-5

32. Banafshe HR, Mesdaghinia A, Arani MN, Ramezani MH, Heydari A, Hamidi GA. Lithium attenuates pain-related behavior in a rat model of neuropathic pain: possible involvement of opioid system. Pharm Biochem Behav. 2012; 100(3): 425-430. doi: 10.1016/j.pbb.2011.10.004

33. De Gandarias JM, Acebes I, Echevarrıa E, Vegas L, Abecia LC, Casis L. Lithium alters mu-opioid receptor expression in the rat brain. Neurosci Lett. 2000; 279(1): 9-12.

34. Мазо Г.Э., Незнанов Н.Г. Терапевтически резистентные депрессии. Санкт-Петербург: Изд-во «Береста»; 2012.

35. Fakhri H, Pathare G, Fajol A, Zhang B, Bock T, Kandolf R, Schleicher E, Biber J, Föller M, Lang UE, Lang F. Regulation of mineral metabolism by lithium. Pflugers Arch. 2014; 466(3): 467-475. doi: 10.1007/s00424-013-1340-y

36. Mellerup ET, Plenge P, Vendsborg P, Rafaelsen OJ, Kjeldsen H, Agerbaek H. Antidiabetic effects of lithium. Lancet. 1972; 300(7791): 1367-1368. doi: 10.1016/S0140-6736(72)92811-5

37. Li L, Li X, Zhou W, Messina JL. Acute psychological stress results in the rapid development of insulin resistance. J Endocrinol. 2013; 217(2): 175-184. doi: 10.1530/JOE-12-0559

38. Li L, Shelton RC, Chassan RA, Hammond JC, Gower BA, Garvey TW. Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity. J Diabetes Metab. 2016; 7(4): pii:664. doi: 10.4172/2155-6156.1000664

39. Misiuta IE, Saporta S, Sanberg PR, Zigova T, Willing AE. Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells. J Neurosci Res. 2006; 83(4): 668-679. doi: 10.1002/jnr.20718

40. Geoffroy PA, Samalin L, Llorca PM, Curis E, Bellivier F. Influence of lithium on sleep and chronotypes in remitted patients with bipolar disorder. J Affect Disord. 2016; 204: 32-39. doi: 10.1016/j.jad.2016.06.015

41. Moreira J, Geoffroy PA. Lithium and bipolar disorder: Impacts from molecular to behavioural circadian rhythms. Chronobiol Int. 2016; 33(4): 351-373. doi: 10.3109/07420528.2016.1151026

42. Lerer B. Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium. Biol Psychiatry. 1985; 20(1): 20-40. doi:10.1016/0006-3223(85)90132-5

43. Wu YY, Wang X, Tan L, Liu D, Liu XH, Wang Q, Wang JZ, Zhu LQ. Lithium attenuates scopolamine-induced memory deficits with inhibition of GSK-3β and preservation of postsynaptic components. J Alzheimers Dis. 2013; 37(3): 515-527. doi: 10.3233/JAD-130521

44. Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR. Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test. Eur Neuropsychopharmacol. 2008; 18(5), 323-332. doi: 10.1016/j.euroneuro.2007.07.011

45. Ghasemi M, Sadeghipour H, Poorheidari G, Dehpour AR. A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test. Behav Brain Res. 2009; 200(1): 76-82. doi: 10.1016/j.bbr.2008.12.032

46. Ghasemi M, Raza M, Dehpour AR. NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. J Psychopharmacol. 2010; 24(4): 585-594. doi: 10.1177/0269881109104845

47. Montezinho LB, Duarte C, Fonseca CP, Glinka Y, Layden B, Mota de Freitas D, Geraldes CF, Castro MM. Intracellular lithium and cyclic AMP levels are mutually regulated in neuronal cells. J Neurochem. 2004; 90(4): 920-930. doi: 10.1111/j.1471-4159.2004.02551.x

48. Machado-Vieira R, Manji HK, Zarate CA. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord. 2009; 11: 92-109. doi: 10.1111/j.1399-5618.2009.00714.x

49. Einat H, Kofman O, Itkin O, Lewitan RJ, Belmaker RH. Augmentation of lithium’s behavioral effect by inositol uptake inhibitors. J Neural Transm, 1998; 105(1): 31-38. doi: 10.1007/s007020050035

50. Patel S, Yenush L, Rodrıguez PL, Serrano R, Blundell TL. Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3′-phosphoadenosine-5′-phosphate phosphatase activities: a novel target of lithium therapy. J Mol Biol. 2002; 315(4): 677-685. doi: 10.1006/jmbi.2001.5271

51. Jope RS. Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry. 1999; 4(2): 117-128. doi: 10.1038/sj.mp.4000494

52. Cechinel-Recco K, Valvassori SS, Varela RB, Resende WR, Arent CO, Vitto MF, Luz G, de Souza CT, Quevedo J. Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania. J Psychopharmacol. 2012; 26(12): 1594-1604. doi: 10.1177/0269881112463124

53. Herlin T, Fogh K, Christiansen NO, Kragballe K. Effect of auranofin on eicosanoids and protein kinase C in human neutrophils. Agents Actions. 1989; 28(1-2): 121-129.

54. Hu B, Wu Y, Liu J, Shen X, Tong F, Xu G, Shen R. GSK-3beta inhibitor induces expression of Nrf2/TrxR2 signaling pathway to protect against renal ischemia/reperfusion injury in diabetic rats. Kidney Blood Press Res. 2016; 41(6): 937-946. doi: 10.1159/000452598

55. Shaltiel G, Deutsch J, Rapoport SI, Basselin M, Belmaker RH, Agam G. Is phosphoadenosine phosphate phosphatase a target of lithium’s therapeutic effect? J Neural Transm. 2009; 116(11): 1543. doi: 10.1007/s00702-009-0298-6

56. Yenush L, Bellés JM, López-Coronado JM, Gil-Mascarell R, Serrano R, Rodríguez PL. A novel target of lithium therapy. FEBS Lett. 2000; 467(2-3): 321-325. doi: 10.1016/S0014-5793(00)01183-2

57. York JD, Ponder JW, Majerus PW. Definition of a metal-dependent/Li (+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. Proc Natl Acad Sci USA. 1995; 92(11): 5149-5153. doi: 10.1073/pnas.92.11.5149

58. López-Coronado JM, Bellés JM, Lesage F, Serrano R, Rodrіguez PL. A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3′-phosphoadenosine 5′-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. J Biol Chem. 1999; 274(23): 16034-16039.

59. Toledano E, Ogryzko V, Danchin A, Ladant D, Mechold U. 3′-5′phosphoadenosine phosphate is an inhibitor of PARP-1 and a potential mediator of the lithium-dependent inhibition of PARP-1 in vivo. Biochem J. 2012; 443(2): 485-490. doi: 10.1042/BJ20111057

60. Boggs DR, Joyce RA. The hematopoietic effects of lithium. Semin Hematol. 1983; 20(2): 129-138.

61. Brewerton TD. Lithium counteracts carbamazepine-induced leukopenia while increasing its therapeutic effect. Biol Psychiatry. 1986; 21(7): 677-685. doi: 10.1016/0006-3223(86)90130-7

62. Lyman GH, Williams CC, Preston D. The use of lithium carbonate to reduce infection and leukopenia during systemic chemotherapy. N Engl J Med. 1980; 302(5): 257-260. doi: 10.1056/NEJM198001313020503

63. Li HJ, Gao DS, Li YT, Wang YS, Liu HY, Zhao J. Antiviral effect of lithium chloride on porcine epidemic diarrhea virus in vitro. Res Vet Sci. 2018; 118: 288-294. doi: 10.1016/j.rvsc.2018.03.002

64. Zhao FR, Xie YL, Liu ZZ, Shao JJ, Li SF, Zhang YG, Chang HY. Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro. J Med Virol. 2017; 89(11): 2041-2046

65. Harrison SM, Tarpey I, Rothwell L, Kaiser P, Hiscox JA. Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture. Avian Pathol. 2007; 36(2): 109-114. doi: 10.1080/03079450601156083

66. Li J, Yin J, Sui X, Li G, Ren X. Comparative analysis of the effect of glycyrrhizin diammonium and lithium chloride on infectious bronchitis virus infection in vitro. Avian Pathol. 2009; 38(3): 215-221. doi: 10.1080/03079450902912184

67. Rybakowski JK. Antiviral and immunomodulatory effect of lithium. Pharmacopsychiatry. 2000; 33(5): 159-164.

68. Canli T. Reconceptualizing major depressive disorder as an infectious disease. Biol Mood Anxiety Disord. 2014; 4: 10. doi: 10.1186/2045-5380-4-10

69. Cussotto S, Strain CR, Fouhy F, Strain RG, Peterson VL, Clarke G, Stanton C, Dinan TG, Cryan GF. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. J Psychopharm. 2018. doi: 10.1007/s00213-018-5006-5

70. Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, Wang W, Tang W, Tan Z, Shi J, Li L, Ruan B. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015; 48: 186-194. doi: 10.1016/j.bbi.2015.03.016

71. Kunugi H. Depressive Disorder and Gut-brain Interaction. Brain Nerve. 2016; 68(6): 641-646. doi: 10.11477/mf.1416200455

72. Lv F, Chen S, Wang L, Jiang R, Tian H, Li J, Yao Y, Zhuo C. The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option. Oncotarget. 2017; 8(59): 100899-100907. doi: 10.18632/oncotarget.21284

73. Soares JC, Gershon S. The psychopharmacologic specificity of the lithium ion: origins and trajectory. J Clin Psychiatry. 2000; 61 (Suppl 9): 16-22.

74. Auzmendi J, Buchholz B, Salguero J, Cañellas C, Kelly J, Men P, Zubillaga M, Rossi A, Merelli A, Gelpi RJ, Ramos AJ, Lazarowski A. Pilocarpine-induced status epilepticus is associated with P-glycoprotein induction in cardiomyocytes, electrocardiographic changes, and sudden death. Pharmaceuticals. 2018; 11(1): 21. doi: 10.3390/ph11010021

75. Hao Y, Wu X, Xu L, Guan Y, Hong Z. MK-801 prevents overexpression of multidrug resistance protein 2 after status epilepticus. Neurol Res. 2012; 34(5): 430-438. doi: 10.1179/1743132811Y.0000000055

76. Ikarashi N, Kagami M, Kobayashi Y, Ishii M, Toda T, Ochiai W, Sugiyama K. Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice. Xenobiotica, 2011; 41(6): 486-493. doi: 10.3109/00498254.2011.551848

77. Bargou RC, Jürchott K, Wagener C, Bergmann S, Metzner S, Bommert K, Mapara MY, Winzer KJ, Dietel M, Dörken B, Royer HD. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat Med. 1997; 3(4): 447-450.

78. Zhou G, Kuo MT. NF-kappaB-mediated induction of mdr1b expression by insulin in rat hepatoma cells. J Biol Chem. 1997; 272(24): 15174-15183. doi: 10.1074/jbc.272.24.15174

79. Lim JC, Kania KD, Wijesuriya H, Chawla S, Sethi JK, Pulaski L, Romero IA, Couraud PO, Weksler BB, Hladky SB, Barrand MA. Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells. J Neurochem. 2008; 106(4): 1855-1865. doi: 10.1111/j.1471-4159.2008.05537.x

80. Yang JM, Vassil AD, Hait WN. Activation of phospholipase C induces the expression of the multidrug resistance (MDR1) gene through the Raf-MAPK pathway. Mol Pharmacol. 2001; 60(4): 674-680.

81. Lu F, Hou YQ, Song Y, Yuan ZJ. TFPI-2 Downregulates Multidrug Resistance Protein in 5-FU-Resistant Human Hepatocellular Carcinoma BEL-7402/5-FU Cells. Anat Rec. 2013; 296(1): 56-63. doi: 10.1002/ar.22611

82. Bark H, Choi CH. PSC833, cyclosporine analogue, downregulates MDR1 expression by activating JNK/c-Jun/AP-1 and suppressing NF-kappaB. Cancer Chemother Pharmacol. 2010; 65(6): 1131-1136. doi: 10.1007/s00280-009-1121-7

83. Sui H, Cai GX, Pan SF, Deng WL, Wang YW, Chen ZS, Cai SJ, Zhu HR, Li Q. miR-200c attenuates P-gp mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther. 2014; 13(12): 3137-3151. doi: 10.1158/1535-7163.MCT-14-0167

84. Newman SA, Pan Y, Short JL, Nicolazzo JA. Assessing the Impact of Lithium Chloride on the Expression of P-Glycoprotein at the Blood-Brain Barrier. J Pharm Sci. 2017; 106(9): 2625-2631. doi: 10.1016/j.xphs.2017.01.013