A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity

Jinhua       Wen; Darrell       Sawmiller; Brendan       Wheeldon; Jun       Tan
Abstract

Lithium as a mood stabilizer has been used as the standard pharmacological treatment for Bipolar Disorder (BD) for more than 60 years. Recent studies have also shown that it has the potential for the treatment of many other neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease, through its neurotrophic, neuroprotective, antioxidant and anti-inflammatory actions. Therefore, exploring its pharmacokinetic features and designing better lithium preparations are becoming important research topics. We reviewed many studies on the pharmacokinetics, drug design and toxicity of lithium based on recent relevant research from PubMed, Web of Science, Elsevier and Springer databases. Keywords used for searching references were lithium, pharmacology, pharmacokinetics, drug design and toxicity. Lithium is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Its level is initially highest in serum and then is evidently redistributed to various tissue compartments. It is not metabolized and over 95% of lithium is excreted unchanged through the kidney, but different lithium preparations may have different pharmacokinetic features. Lithium has a narrow therapeutic window limited by various adverse effects, but some novel drugs of lithium may overcome these problems. Various formulations of lithium have the potential for treating neurodegenerative brain diseases but further study on their pharmacokinetics will be required in order to determine the optimal formulation, dosage and route of administration.
Keywords: Lithium, pharmacokinetics, pharmacodynamics, toxicity, lithium salts, drug design.
Graphical Abstract

[1] 
Shorter E. The history of lithium therapy. Bipolar Disord  2009; 11(Suppl. 2): 4-9.
[http://dx.doi.org/10.1111/j.1399-5618.2009.00706.x] [PMID:  19538681] 
[2] 
Oruch R, Elderbi MA, Khattab HA, Pryme IF, Lund A. Lithium: A review of pharmacology, clinical uses, and toxicity. Eur J Pharmacol  2014; 740: 464-73.
[http://dx.doi.org/10.1016/j.ejphar.2014.06.042] [PMID:  24991789] 
[3] 
Young W. Review of lithium effects on brain and blood. Cell Transplant  2009; 18(9): 951-75.
[http://dx.doi.org/10.3727/096368909X471251] [PMID:  19523343] 
[4] 
Richardson T, Macaluso M. Clinically relevant treatment considerations regarding lithium use in bipolar disorder. Expert Opin Drug Metab Toxicol  2017; 13(11): 1105-13.
[http://dx.doi.org/10.1080/17425255.2017.1386653] [PMID:  28965429] 
[5] 
Grandjean EM, Aubry JM. Lithium: Updated human knowledge using an evidence-based approach: Part III: Clinical safety. CNS Drugs  2009; 23(5): 397-418.
[http://dx.doi.org/10.2165/00023210-200923050-00004] [PMID:  19453201] 
[6] 
Zhao J, Zhu M, Kumar M, et al. A pharmacological appraisal of neuroprotective and neurorestorative flavonoids against neurodegenerative diseases. CNS Neurol Disord Drug Targets  2019; 18(2): 103-14.
[http://dx.doi.org/10.2174/1871527317666181105093834] [PMID:  30394219] 
[7] 
Mazza M, Marano G, Traversi G, Carocci V, Romano B, Janiri L. Cariprazine in bipolar depression and mania: State of the art. CNS Neurol Disord Drug Targets  2018; 17(10): 723-7.
[http://dx.doi.org/10.2174/1871527317666180828120256] [PMID:  30152291] 
[8] 
D Alessandro J, Garofalo K, Zhao G, et al. Demonstration of biological and immunological equivalence of a generic glatiramer acetate. CNS Neurol Disord Drug Targets  2017; 16(6): 714-23.
[http://dx.doi.org/10.2174/1871527316666170223162747] [PMID:  28240190] 
[9] 
Ehrlich BE, Diamond JM. Lithium, membranes, and manic-depressive illness. J Membr Biol  1980; 52(3): 187-200.
[http://dx.doi.org/10.1007/BF01869189] [PMID:  6991708] 
[10] 
Hunter R. Steady-state pharmacokinetics of lithium carbonate in healthy subjects. Br J Clin Pharmacol  1988; 25(3): 375-80.
[http://dx.doi.org/10.1111/j.1365-2125.1988.tb03316.x] [PMID:  3129009] 
[11] 
Chen C, Veronese L, Yin Y. The effects of lamotrigine on the pharmacokinetics of lithium. Br J Clin Pharmacol  2000; 50(3): 193-5.
[http://dx.doi.org/10.1046/j.1365-2125.2000.00248.x] [PMID:  10971302] 
[12] 
Carman JS, Post RM, Teplitz TA, Goodwin FK. Letter: Divalent cations in predicting antidepressant response to lithium. Lancet  1974; 2(7894): 1454.
[http://dx.doi.org/10.1016/S0140-6736(74)90114-7] [PMID:  4140369] 
[13] 
Lee CF, Yang YY, Hu OY. Single dose pharmacokinetic study of lithium in Taiwanese/Chinese bipolar patients. Aust N Z J Psychiatry  1998; 32(1): 133-6.
[http://dx.doi.org/10.3109/00048679809062720] [PMID:  9565195] 
[14] 
Shelley RK. Are there ethnic differences in lithium pharmacokinetics and side-effects? Int Clin Psychopharmacol  1987; 2(4): 337-42.
[http://dx.doi.org/10.1097/00004850-198710000-00007] [PMID:  3693874] 
[15] 
Wungu TD, Aspera SM, David MY, Dipojono HK, Nakanishi H, Kasai H. Absorption of lithium in montmorillonite: A density functional theory (DFT) study. J Nanosci Nanotechnol  2011; 11(4): 2793-801.
[http://dx.doi.org/10.1166/jnn.2011.3913] [PMID:  21776634] 
[16] 
Ponampalam R, Otten EJ. In vitro adsorption of lithium by bentonite. Singapore Med J  2002; 43(2): 86-9.
[17] 
Moosavi M. Bentonite clay as a natural remedy: A brief review. Iran J Public Health  2017; 46(9): 1176-83.
[PMID:  29026782] 
[18] 
Favin FD, Klein-Schwartz W, Oderda GM, Rose SR. In vitro study of lithium carbonate adsorption by activated charcoal. J Toxicol Clin Toxicol  1988; 26(7): 443-50.
[http://dx.doi.org/10.3109/15563658809038560] [PMID:  3148035] 
[19] 
Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol  1994; 34(4): 280-5.
[http://dx.doi.org/10.1002/j.1552-4604.1994.tb01994.x] [PMID:  8006194] 
[20] 
Habib A, Sawmiller D, Li S, et al. LISPRO mitigates β-amyloid and associated pathologies in Alzheimer’s mice. Cell Death Dis  2017; 8(6): e2880.
[http://dx.doi.org/10.1038/cddis.2017.279] [PMID:  28617434] 
[21] 
Hillert M, Zimmermann M, Klein J. Uptake of lithium into rat brain after acute and chronic administration. Neurosci Lett  2012; 521(1): 62-6.
[http://dx.doi.org/10.1016/j.neulet.2012.05.060] [PMID:  22659074] 
[22] 
Lenox RH, Hahn CG. Overview of the mechanism of action of lithium in the brain: Fifty-year update. J Clin Psychiatry  2000; 61(Suppl. 9): 5-15.
[PMID:  10826655] 
[23] 
Milosavljevic N, Monet M, Léna I, et al. The intracellular Na(+)/H(+) exchanger NHE7 effects a Na(+)-coupled, but not K(+)-coupled proton-loading mechanism in endocytosis. Cell Rep  2014; 7(3): 689-96.
[http://dx.doi.org/10.1016/j.celrep.2014.03.054] [PMID:  24767989] 
[24] 
Maletzky BM. Enhancing the efficacy of lithium treatment by combined use with diuretics and low sodium diets: A preliminary report. J Clin Psychiatry  1979; 40(7): 317-22.
[PMID:  378986] 
[25] 
Machado-Vieira R, Otaduy MC, Zanetti MV, et al. A selective association between central and peripheral lithium levels in remitters in bipolar depression: A 3T-(7) Li magnetic resonance spectroscopy study. Acta Psychiatr Scand  2016; 133(3): 214-20.
[http://dx.doi.org/10.1111/acps.12511] [PMID:  26513535] 
[26] 
Sakae R, Ishikawa A, Niso T, et al. Decreased lithium disposition to cerebrospinal fluid in rats with glycerol-induced acute renal failure. Pharm Res  2008; 25(10): 2243-9.
[http://dx.doi.org/10.1007/s11095-008-9612-5] [PMID:  18581208] 
[27] 
Hanak AS, Chevillard L, El Balkhi S, Risede P, Peoc’h K, Megarbane B. Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning. Toxicol Sci  2015; 143(1): 185-95.
[http://dx.doi.org/10.1093/toxsci/kfu224] [PMID:  25354763] 
[28] 
Suwalsky M, Fierro P, Villena F, Sotomayor CP. Effects of lithium on the human erythrocyte membrane and molecular models. Biophys Chem  2007; 129(1): 36-42.
[http://dx.doi.org/10.1016/j.bpc.2007.05.003] [PMID:  17532553] 
[29] 
Arancibia A, Paulos C, Chávez J, Ritschel WA. Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude. Int J Clin Pharmacol Ther  2003; 41(5): 200-6.
[http://dx.doi.org/10.5414/CPP41200] [PMID:  12776810] 
[30] 
Wilting I, Fase S, Martens EP, Heerdink ER, Nolen WA, Egberts AC. The impact of environmental temperature on lithium serum levels. Bipolar Disord  2007; 9(6): 603-8.
[http://dx.doi.org/10.1111/j.1399-5618.2007.00438.x] [PMID:  17845275] 
[31] 
Nielsen RE, Damkier P. Pharmacological treatment of unipolar depression during pregnancy and breast-feeding--a clinical overview. Nord J Psychiatry  2012; 66(3): 159-66.
[http://dx.doi.org/10.3109/08039488.2011.650198] [PMID:  22283766] 
[32] 
Bogen DL, Sit D, Genovese A, Wisner KL. Three cases of lithium exposure and exclusive breastfeeding. Arch Women Ment Health  2012; 15(1): 69-72.
[http://dx.doi.org/10.1007/s00737-012-0257-3] [PMID:  22277970] 
[33] 
Ahmed I, Yang J, Law AWL, et al. Rapid and in situ optical detection of trace lithium in tissues. Biomed Opt Express  2018; 9(9): 4459-71.
[http://dx.doi.org/10.1364/BOE.9.004459] [PMID:  30615723] 
[34] 
Price LH, Heninger GR. Lithium in the treatment of mood disorders. N Engl J Med  1994; 331(9): 591-8.
[http://dx.doi.org/10.1056/NEJM199409013310907] [PMID:  8047085] 
[35] 
Uwai Y, Kawasaki T, Nabekura T. Minor contribution of biliary excretion in lithium elimination in rats. Drug Metab Pers Ther  2015; 30(1): 65-7.
[http://dx.doi.org/10.1515/dmdi-2014-0033] [PMID:  25803094] 
[36] 
Brager NP, Campbell NR, Reisch H, Chaudhuri M, Rabin HR. Reduced renal fractional excretion of lithium in cystic fibrosis. Br J Clin Pharmacol  1996; 41(2): 157-9.
[http://dx.doi.org/10.1111/j.1365-2125.1996.tb00174.x] [PMID:  8838443] 
[37] 
Aronson JK, Reynolds DJ. ABC of monitoring drug therapy. Lithium. BMJ  1992; 305(6864): 1273-6.
[http://dx.doi.org/10.1136/bmj.305.6864.1273] [PMID:  1477574] 
[38] 
Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry  1995; 37(5): 348-50.
[http://dx.doi.org/10.1016/0006-3223(94)00243-V] [PMID:  7748990] 
[39] 
Shirley DG, Walter SJ, Noormohamed FH. Natriuretic effect of caffeine: Assessment of segmental sodium reabsorption in humans. Clin Sci (Lond)  2002; 103(5): 461-6.
[http://dx.doi.org/10.1042/cs1030461] [PMID:  12401118] 
[40] 
Caraci F, Sultana J, Drago F, Spina E. Clinically relevant drug interactions with anti-Alzheimer’s drugs. CNS Neurol Disord Drug Targets  2017; 16(4): 501-13.
[http://dx.doi.org/10.2174/1871527316666170303144817] [PMID:  28260511] 
[41] 
Arellano AL, Papaseit E, Romaguera A, Torrens M, Farré M. Neuropsychiatric and general interactions of natural and synthetic Cannabinoids with drugs of abuse and medicines. CNS Neurol Disord Drug Targets  2017; 16(5): 554-66.
[http://dx.doi.org/10.2174/1871527316666170413104516] [PMID:  28412920] 
[42] 
Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF. Does lithium prevent Alzheimer’s disease? Drugs Aging  2012; 29(5): 335-42.
[http://dx.doi.org/10.2165/11599180-000000000-00000] [PMID:  22500970] 
[43] 
Emami J, Tavakoli N, Movahedian A. Formulation of sustained - release lithium carbonate matrix tablets: Influence of hydrophilic materials on the release rate and in vitro-in vivo evaluation. J Pharm Pharm Sci  2004; 7(3): 338-44.
[PMID:  15576014] 
[44] 
Haddad LM, Winchester JF. Clinical management of poisoning and drug overdose.  2nd ed. Philadelphia, PA: WB Saunders;.  1990; 2: pp. 656-65.
[45] 
Persson G. Plasma lithium levels and side effects during administration of a slow release lithium sulphate preparation (Lithium lipett C) and lithium carbonate tablets. Acta Psychiatr Scand  1974; 50(2): 174-82.
[http://dx.doi.org/10.1111/j.1600-0447.1974.tb08206.x] [PMID:  4853671] 
[46] 
Kolk A, Kathmann N, Greil W. No short-term changes of cognitive performance and mood after single doses of two different lithium retard preparations. Pharmacopsychiatry  1993; 26(6): 235-9.
[http://dx.doi.org/10.1055/s-2007-1014360] [PMID:  8127927] 
[47] 
Ozawa H, Nozu T, Aihara H, Akiyama F, Sasajima M. [Pharmacokinetics and general pharmacological actions of lithium salts administered singly or repeatedly Nippon Yakurigaku Zasshi  1976; 72(4): 433-43.
[PMID:  987975] 
[48] 
Smith DF. Lithium orotate, carbonate and chloride: pharmacokinetics, polydipsia and polyuria in rats. Br J Pharmacol  1976; 56(4): 399-402.
[http://dx.doi.org/10.1111/j.1476-5381.1976.tb07449.x] [PMID:  1260219] 
[49] 
Altamura AC, Gomeni R, Sacchetti E, Smeraldi E. Plasma and intracellular kinetics of lithium after oral administration of various lithium salts. Eur J Clin Pharmacol  1977; 12(1): 59-63.
[http://dx.doi.org/10.1007/BF00561406] [PMID:  902676] 
[50] 
Devadason P. Is there a role for lithium orotate in psychiatry? Aust N Z J Psychiatry 2018.: 4867418810185.
[http://dx.doi.org/10.1177/0004867418810185] [PMID:  30404535] 
[51] 
Nieper HA. The clinical applications of lithium orotate. A two years study. Agressologie  1973; 14(6): 407-11.
[PMID:  4607169] 
[52] 
Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. J Pharm Pharmacol  1978; 30(6): 368-70.
[http://dx.doi.org/10.1111/j.2042-7158.1978.tb13258.x] [PMID:  26768] 
[53] 
Smith DF, Schou M. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. J Pharm Pharmacol  1979; 31(3): 161-3.
[http://dx.doi.org/10.1111/j.2042-7158.1979.tb13461.x] [PMID:  34690] 
[54] 
Smith AJ, Kim SH, Tan J, et al. Plasma and brain pharmacokinetics of previously unexplored lithium salts. RSC Advances  2014; 4(24): 12362-5.
[http://dx.doi.org/10.1039/C3RA46962J] [PMID:  25045517] 
[55] 
Ciftçi K, Capan Y, Oztürk O, Hincal AA. Formulation and in vitro-in vivo evaluation of sustained-release lithium carbonate tablets. Pharm Res  1990; 7(4): 359-63.
[http://dx.doi.org/10.1023/A:1015863204732] [PMID:  2114020] 
[56] 
Vismari L, Pires MLN, Benedito-Silva AA, Calil HM. Bioavailability of immediate and controlled release formulations of lithium carbonate. Rev Bras Psiquiatr  2002; 24(2): 74-9.
[http://dx.doi.org/10.1590/S1516-44462002000200007] 
[57] 
Smith AJ, Kim SH, Duggirala NK, et al. Improving lithium therapeutics by crystal engineering of novel ionic cocrystals. Mol Pharm  2013; 10(12): 4728-38.
[http://dx.doi.org/10.1021/mp400571a] [PMID:  24191685] 
[58] 
Wilson EN, Do Carmo S, Iulita MF, et al. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology. Transl Psychiatry  2017; 7(8): e1190.
[http://dx.doi.org/10.1038/tp.2017.169] [PMID:  28763060] 
[59] 
Geeva NS, Narayan S. Lithium entrapped chitosan nanoparticles to reduce toxicity and increase cellular uptake of lithium. Environ Toxicol Pharmacol  2018; 61: 79-86.
[http://dx.doi.org/10.1016/j.etap.2018.05.017] [PMID:  29852373] 
[60] 
Bruch GE, Cordeiro MF, Gomides LS, et al. Implications of PEGylation of carbon nanotubes for central nervous system bioavailability. CNS Neurol Disord Drug Targets  2017; 16(9): 983-9.
[PMID:  28758581] 
[61] 
Sarkar S, Floto RA, Berger Z, et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol  2005; 170(7): 1101-11.
[http://dx.doi.org/10.1083/jcb.200504035] [PMID:  16186256] 
[62] 
Fornai F, Longone P, Ferrucci M, et al. Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium. Autophagy  2008; 4(4): 527-30.
[http://dx.doi.org/10.4161/auto.5923] [PMID:  18367867] 
[63] 
Le Roy V, Delmas Y, Verdoux H. Chronic renal complications induced by lithium. Encephale  2009; 35(6): 605-10.
[http://dx.doi.org/10.1016/j.encep.2008.12.007] [PMID:  20004292] 
[64] 
Schmitt C, Furet Y, Perrotin D, Paintaud G. Acute lithium intoxications, review of the literature and cases study. Therapie  2009; 64(1): 55-63.
[http://dx.doi.org/10.2515/therapie/2009010] [PMID:  19463253] 
[65] 
Kerckhoffs APM, Hartong EGTM, Grootens KP. The perspectives of patients with lithium-induced end-stage renal disease. Int J Bipolar Disord  2018; 6(1): 13.
[http://dx.doi.org/10.1186/s40345-018-0121-0] [PMID:  29858927] 
[66] 
Gitlin M. Lithium and the kidney: An updated review. Drug Saf  1999; 20(3): 231-43.
[http://dx.doi.org/10.2165/00002018-199920030-00004] [PMID:  10221853] 
[67] 
Azab AN, Shnaider A, Osher Y, Wang D, Bersudsky Y, Belmaker RH. Lithium nephrotoxicity. Int J Bipolar Disord  2015; 3(1): 28.
[http://dx.doi.org/10.1186/s40345-015-0028-y] [PMID:  26043842] 
[68] 
Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. End-stage renal disease associated with prophylactic lithium treatment. Eur Neuropsychopharmacol  2014; 24(4): 540-4.
[http://dx.doi.org/10.1016/j.euroneuro.2014.01.002] [PMID:  24503277] 
[69] 
Nielsen J, Kwon TH, Frøkiaer J, Knepper MA, Nielsen S. Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD. Am J Physiol Renal Physiol  2006; 290(5): F1222-33.
[http://dx.doi.org/10.1152/ajprenal.00321.2005] [PMID:  16332930] 
[70] 
Christensen BM, Zuber AM, Loffing J, et al. alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol  2011; 22(2): 253-61.
[http://dx.doi.org/10.1681/ASN.2010070734] [PMID:  21051735] 
[71] 
El-Sheikh AAK, Kamel MY. Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity: Differential regulation of COX-2/PGE2 pathway. Biomed Pharmacother  2016; 84: 1873-84.
[PMID:  27847198] 
[72] 
Lazarus JH, John R, Bennie EH, Chalmers RJ, Crockett G. Lithium therapy and thyroid function: A long-term study. Psychol Med  1981; 11(1): 85-92.
[http://dx.doi.org/10.1017/S0033291700053307] [PMID:  6782599] 
[73] 
Rizwan MM, Perrier ND. Long-term lithium therapy leading to hyperparathyroidism: A case report. Perspect Psychiatr Care  2009; 45(1): 62-5.
[http://dx.doi.org/10.1111/j.1744-6163.2009.00201.x] [PMID:  19154241] 
[74] 
Gutgesell H. Lithium use in pregnancy and the risk of cardiac malformations. N Engl J Med  2017; 377(9): 893.
[http://dx.doi.org/10.1056/NEJMc1708919] [PMID:  28858463] 
[75] 
Chadha VD, Bhalla P, Dhawan D. Uptake and retention of 65Zn in lithium-treated rat liver: Role of zinc. Dig Liver Dis  2010; 42(6): 446-50.
[PMID:  19766547] 
[76] 
Halboos A, Jockenhovel F. Complete atrioventricular block during lithium therapy within therapeutic range. Dtsch Med Wochenschr  2012; 137(49): 2583-5.
[PMID:  23188641] 
[77] 
Forester BP, Streeter CC, Berlow YA, et al. Brain lithium levels and effects on cognition and mood in geriatric bipolar disorder: A lithium-7 magnetic resonance spectroscopy study. Am J Geriatr Psychiatry  2009; 17(1): 13-23.
[http://dx.doi.org/10.1097/JGP.0b013e318172b3d0] [PMID:  18626002] 
[78] 
Nielsen RE, Kessing LV, Nolen WA, Licht RW. Lithium and renal impairment: A review on a still hot topic. Pharmacopsychiatry  2018; 51(5): 200-5.
[http://dx.doi.org/10.1055/s-0043-125393] [PMID:  29346806] 
[79] 
Medić B, Stojanović M, Štimec B, et al. Lithium - pharmacological and toxicological aspects: The current state of the art. Curr Med Chem 2018.
[PMID:  30182841] 
[80] 
Guidi S, Bianchi P, Stagni F, et al. Lithium restores age-related olfactory impairment in the Ts65Dn mouse model of down syndrome. CNS Neurol Disord Drug Targets  2017; 16(7): 812-9.
[http://dx.doi.org/10.2174/1871527315666160801143108] [PMID:  27488422] 
[81] 
Luo Q, Ren Z, Zhu L, et al. Involvement of microRNA-146a in the inflammatory response of status Epilepticus Rats. CNS Neurol Disord Drug Targets  2017; 16(6): 686-93.
[http://dx.doi.org/10.2174/1871527316666170505123956] [PMID:  28474544] 
[82] 
Jiang XW, Lu HY, Xu Z, et al. In Silico analyses for key genes and molecular genetic mechanism in epilepsy and Alzheimer’s disease. CNS Neurol Disord Drug Targets  2018; 17(8): 608-17.
[http://dx.doi.org/10.2174/1871527317666180724150839] [PMID:  30047339] 
[83] 
Rapoport SI. Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade. ACS Chem Neurosci  2014; 5(6): 459-67.
[http://dx.doi.org/10.1021/cn500058v] [PMID:  24786695] 
[84] 
Kamal MA, Shakil S, Nawaz MS, et al. Inhibition of butyrylcholinesterase with fluorobenzylcymserine, an experimental Alzheimer’s drug candidate: Validation of enzoinformatics results by classical and innovative enzyme kinetic analyses. CNS Neurol Disord Drug Targets  2017; 16(7): 820-7.
[http://dx.doi.org/10.2174/1871527316666170207160606] [PMID:  28176640] 
Cite As
CNS & Neurological Disorders - Drug Targets

A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity

Abstract

Graphical Abstract
