Research Article

Standardizing the Effective Correlated Dosage of Olanzapine and Empagliflozin in Female Wistar Rats

Author(s): Ghulam Md. Ashraf*, Badrah S. Alghamdi, Fahad S. Alshehri, Mohammad Z. Alam, Haythum O. Tayeb and Frank I. Tarazi

Volume 21, Issue 1, 2021

Published on: 11 November, 2020

Page: [53 - 59] Pages: 7

DOI: 10.2174/1566523220999201111195047

Price: $65

Abstract

Aim: The primary aim of this study was to standardize the correlated effective dosage of the antidiabetic drug empagliflozin (EMPA) and the antipsychotic drug olanzapine (Ola).

Background: Atypical antipsychotics are associated with BWG and metabolic disturbances for which many approaches have been used to minimize these issues, including antidiabetic drugs. The antidiabetic drugs have been quite effective in reversing BWG induced by the administration of antipsychotic drugs in patients who have psychosis, schizophrenia and bipolar disorder.

Objective: The objective of this study was to standardize the correlated effective dosage of EMPA and Ola.

Methods: The study was carried out for 28 days to represent the chronic effect of Ola on female Wistar rats. Rats were divided into three groups based on the dose they received: control (vehicle), Ola-4 and Ola-8 (4 and 8 mg/kg/OD, respectively), and EMPA-10 and EMPA-20 (10 and 20 mg/kg/OD, respectively).

Results: Both doses of Ola produced a significant increase in the percentage of BWG, however, Ola-4 produced a higher BWG. Also, both the doses of EMPA were able to reverse the effect of Ola-induced BWG; however, EMPA-20 produced a higher reversal in BWG and normalized the rat's body weight.

Conclusion: We conclude that Ola-4 and EMPA-20 were the most effective dosage for experimental purposes in female Wistar rats. The findings of this study standardized the effective correlated dosage of olanzapine and empagliflozin in female Wistar rats that will help understand the underlying molecular and behavioral mechanisms.

Keywords: Antidiabetics, antipsychotics, body weight gain, empagliflozin, female wistar rats, olanzapine.

Graphical Abstract
[1]
Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand 1999; 100(1): 3-16.
[http://dx.doi.org/10.1111/j.1600-0447.1999.tb10908.x] [PMID: 10442434]
[2]
Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat 2017; 13: 2231-41.
[http://dx.doi.org/10.2147/NDT.S113099] [PMID: 28883731]
[3]
Barton BB, Segger F, Fischer K, Obermeier M, Musil R. Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf 2020; 19(3): 295-314.
[http://dx.doi.org/10.1080/14740338.2020.1713091] [PMID: 31952459]
[4]
Werneke U, Taylor D, Sanders TAB. Behavioral interventions for antipsychotic induced appetite changes. Curr Psychiatry Rep 2013; 15(3): 347.
[http://dx.doi.org/10.1007/s11920-012-0347-y] [PMID: 23404388]
[5]
Tungaraza TE. Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject. Ther Adv Psychopharmacol 2016; 6(5): 335-42.
[http://dx.doi.org/10.1177/2045125316649534] [PMID: 27721972]
[6]
Papanastasiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review. Ther Adv Psychopharmacol 2013; 3(1): 33-51.
[http://dx.doi.org/10.1177/2045125312464385] [PMID: 23983991]
[7]
Xu H, Zhuang X. Atypical antipsychotics-induced metabolic syndrome and nonalcoholic fatty liver disease: a critical review. Neuropsychiatr Dis Treat 2019; 15: 2087-99.
[http://dx.doi.org/10.2147/NDT.S208061] [PMID: 31413575]
[8]
Javed A, Arthur H, Curtis L, Hansen L, Pappa S. Practical guidance on the use of lurasidone for the treatment of adults with schizophrenia. Neurol Ther 2019; 8(2): 215-30.
[http://dx.doi.org/10.1007/s40120-019-0138-z] [PMID: 31098889]
[9]
Khan UA, Parveen U, Hasan N, et al. Parenteral sustained release lipid phase-transition system of ziprasidone: fabrication and evaluation for schizophrenia therapy. Drug Des Devel Ther 2020; 14: 2237-47.
[http://dx.doi.org/10.2147/DDDT.S247196] [PMID: 32606594]
[10]
Citrome L, McEvoy JP, Todtenkopf MS, McDonnell D, Weiden PJ. A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future. Neuropsychiatr Dis Treat 2019; 15: 2559-69.
[http://dx.doi.org/10.2147/NDT.S209284] [PMID: 31564881]
[11]
Mauri MC, Paletta S, Maffini M, et al. Clinical pharmacology of atypical antipsychotics: an update. EXCLI J 2014; 13: 1163-91.
[PMID: 26417330]
[12]
van Baar MJB, van Ruiten CC, Muskiet MHA, van Bloemendaal L, IJzerman RG, van Raalte DH. SGLT2 inhibitors in combination therapy: from mechanisms to clinical considerations in type 2 diabetes management. Diabetes Care 2018; 41(8): 1543-56.
[http://dx.doi.org/10.2337/dc18-0588] [PMID: 30030256]
[13]
Pradhan A, Vohra S, Vishwakarma P, Sethi R. Review on sodium-glucose cotransporter 2 inhibitor (SGLT2i) in diabetes mellitus and heart failure. J Family Med Prim Care 2019; 8(6): 1855-62.
[http://dx.doi.org/10.4103/jfmpc.jfmpc_232_19] [PMID: 31334145]
[14]
Tarazi FI, Zhang K, Baldessarini RJ. Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: implications for antipsychotic drug treatment. J Pharmacol Exp Ther 2001; 297(2): 711-7.
[PMID: 11303062]
[15]
Kurbanov DB, Currie PJ, Simonson DC, Borsook D, Elman I. Effects of naltrexone on food intake and body weight gain in olanzapine-treated rats. J Psychopharmacol 2012; 26(9): 1244-51.
[http://dx.doi.org/10.1177/0269881112450783] [PMID: 22723540]
[16]
Mathews J, Newcomer JW, Mathews JR, et al. Neural correlates of weight gain with olanzapine. Arch Gen Psychiatry 2012; 69(12): 1226-37.
[http://dx.doi.org/10.1001/archgenpsychiatry.2012.934] [PMID: 22868896]
[17]
Okazaki K, Yamamuro K, Kishimoto T. Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report. Neuropsychiatr Dis Treat 2017; 13: 2837-40.
[http://dx.doi.org/10.2147/NDT.S148616] [PMID: 29200857]
[18]
Lord CC, Wyler SC, Wan R, et al. The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C. J Clin Invest 2017; 127(9): 3402-6.
[http://dx.doi.org/10.1172/JCI93362] [PMID: 28805659]
[19]
Neeland IJ, McGuire DK, Chilton R, et al. Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. Diab Vasc Dis Res 2016; 13(2): 119-26.
[http://dx.doi.org/10.1177/1479164115616901] [PMID: 26873905]
[20]
Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs 2019; 79(3): 219-30.
[http://dx.doi.org/10.1007/s40265-019-1057-0] [PMID: 30701480]
[21]
Vickers SP, Cheetham SC, Headland KR, et al. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet. Diabetes Metab Syndr Obes 2014; 7: 265-75.
[http://dx.doi.org/10.2147/DMSO.S58786] [PMID: 25061325]
[22]
Ganguli R. Weight gain associated with antipsychotic drugs. J Clin Psychiatry 1999; 60(21): 20-4.
[PMID: 10548138]
[23]
Bhana N, Foster RH, Olney R, Plosker GL. Olanzapine: an updated review of its use in the management of schizophrenia. Drugs 2001; 61(1): 111-61.
[http://dx.doi.org/10.2165/00003495-200161010-00011] [PMID: 11217867]
[24]
Raskind MA, Burke BL, Crites NJ, Tapp AM, Rasmussen DD. Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats. Neuropsychopharmacology 2007; 32(2): 284-8.
[http://dx.doi.org/10.1038/sj.npp.1301093] [PMID: 16710316]
[25]
Fernø J, Varela L, Skrede S, et al. Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLoS One 2011; 6(6: )e20571.
[http://dx.doi.org/10.1371/journal.pone.0020571] [PMID: 21695181]
[26]
Park S, Hong SM, Ahn ILS, Kim DS, Kim SH. Estrogen replacement reverses olanzapine-induced weight gain and hepatic insulin resistance in ovariectomized diabetic rats. Neuropsychobiology 2010; 61(3): 148-61.
[http://dx.doi.org/10.1159/000285780] [PMID: 20173353]
[27]
Kim SF, Huang AS, Snowman AM, Teuscher C, Snyder SH, Snyder SH. From the cover: antipsychotic drug-induced weight gain mediated by histamine h1 receptor-linked activation of hypothalamic amp-kinase. Proc Natl Acad Sci USA 2007; 104(9): 3456-9.
[http://dx.doi.org/10.1073/pnas.0611417104] [PMID: 17360666]
[28]
Cooper GD, Pickavance LC, Wilding JP, Halford JC, Goudie AJ. A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology (Berl) 2005; 181(1): 80-9.
[http://dx.doi.org/10.1007/s00213-005-2224-4] [PMID: 15778884]
[29]
Kalinichev M, Rourke C, Daniels AJ, et al. Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats. Psychopharmacology (Berl) 2005; 182(2): 220-31.
[http://dx.doi.org/10.1007/s00213-005-0081-9] [PMID: 16001110]
[30]
Weston-Green K, Huang XF, Deng C. Sensitivity of the female rat to olanzapine-induced weight gain--far from the clinic? Schizophr Res 2010; 116(2-3): 299-300.
[http://dx.doi.org/10.1016/j.schres.2009.09.034] [PMID: 19840894]
[31]
Sejima E, Yamauchi A, Nishioku T, et al. A role for hypothalamic AMP-activated protein kinase in the mediation of hyperphagia and weight gain induced by chronic treatment with olanzapine in female rats. Cell Mol Neurobiol 2011; 31(7): 985-9.
[http://dx.doi.org/10.1007/s10571-011-9663-8] [PMID: 21681559]
[32]
He M, Zhang Q, Deng C, Wang H, Lian J, Huang XF. Hypothalamic histamine H1 receptor-AMPK signaling time-dependently mediates olanzapine-induced hyperphagia and weight gain in female rats. Psychoneuroendocrinology 2014; 42: 153-64.
[http://dx.doi.org/10.1016/j.psyneuen.2014.01.018] [PMID: 24636512]
[33]
Choi S, DiSilvio B, Unangst J, Fernstrom JD. Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats. Life Sci 2007; 81(12): 1024-30.
[http://dx.doi.org/10.1016/j.lfs.2007.08.009] [PMID: 17822717]
[34]
Cooper GD, Pickavance LC, Wilding JP, Harrold JA, Halford JC, Goudie AJ. Effects of olanzapine in male rats: enhanced adiposity in the absence of hyperphagia, weight gain or metabolic abnormalities. J Psychopharmacol 2007; 21(4): 405-13.
[http://dx.doi.org/10.1177/0269881106069637] [PMID: 17050655]
[35]
Lykkegaard K, Larsen PJ, Vrang N, Bock C, Bock T, Knudsen LB. The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance. Schizophr Res 2008; 103(1-3): 94-103.
[http://dx.doi.org/10.1016/j.schres.2008.05.011] [PMID: 18579346]
[36]
Hu Y, Young AJ, Ehli EA, et al. Metformin and berberine prevent olanzapine-induced weight gain in rats. PLoS One 2014; 9(3: )e93310.
[37]
Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Nizatidine treatment and its relationship with leptin levels in patients with olanzapine-induced weight gain. Hum Psychopharmacol 2003; 18(6): 457-61.
[http://dx.doi.org/10.1002/hup.514] [PMID: 12923824]
[38]
Lian J, Huang XF, Pai N, Deng C. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment. PLoS One 2014; 9(8: )e104160.
[http://dx.doi.org/10.1371/journal.pone.0104160] [PMID: 25084453]
[39]
Razavi BM, Lookian F, Hosseinzadeh H. Protective effects of green tea on olanzapine-induced-metabolic syndrome in rats. Biomed Pharmacother 2017; 92: 726-31.
[http://dx.doi.org/10.1016/j.biopha.2017.05.113] [PMID: 28586744]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy