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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Chemistry, Analysis, Pharmacokinetics and Pharmacodynamics Aspects of Lorcaserin, a Selective Serotonin 5-HT2C Receptor Agonist: An Update

Author(s): Sanjay Sharma *, Komal S. Aware, Ketan Hatware and Kiran Patil

Volume 20 , Issue 9 , 2020

Page: [768 - 778] Pages: 11

DOI: 10.2174/1389557519666190408154443

Price: $65


This review refers to the all-inclusive details of Lorcaserin Hydrochloride on comprehensive information about the synthesis, analytical methods, pharmacodynamics, pharmacokinetics, drug interactions and adverse effects. Lorcaserin Hydrochloride is chemically (R)-8-Chloro-1-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine hydrochloride. Lorcaserin HCl is a novel, synthetic, centrally-acting selective serotonin C (5-HT2c) receptor, l agonist, which results in increased satiety and decreased food consumption in patients. Headache, dizziness and nausea are the most common side effects associated with this drug. Lorcaserin HCl has two major metabolites, one conjugated with glucuronide called N-carbamoyl glucuronide which is excreted in urine and the second Lorcaserin N-sulfamate, which is circulated in the blood. Lorcaserin HCl is synthesized using four different schemes of which a six-step method that resulted in 92.3% yield with 99.8% of purity is employed for scale-up production. It is analyzed quantitatively in the plasma and brain tissue matrix of rats by Ultra Performance Liquid chromatographic (UPLC) method using MS-MS (Mass Spectrometric) detection.

Keywords: Lorcaserin hydrochloride, appetite suppressant, chemistry, analysis, pharmacokinetics, pharmacodynamics.

Graphical Abstract
Asyifah, M.R.; Lu, K.; Ting, H.L.; Zhang, D. Hidden potential of tropical fruit waste components as a useful source of remedy for obesity. J. Agric. Food Chem., 2014, 62(16), 3505-3516.
Christopher, R.; Morgan, M.; Ferry, J.; Rege, B.; Tang, Y.; Kristensen, A.; Shanahan, W. Single and multiple-dose pharmacokinetics of a lorcaserin extended-release tablet. Clin. Ther., 2016, 38(10), 2227-2238.
Kang, J.G.; Park, C. Anti-Obesity drugs: A review about their effects and safety. Diabetes Metab. J., 2012, 36(1), 13-25.
Dixon, J.B. Advances in managing obesity. Nat. Publ. Gr.,, 2016, 2015-2016.
Manning, S.; Pucci, A.; Finer, N. Pharmacotherapy for obesity: Novel agents and paradigms. Ther. Adv. Chronic Dis., 2014, 5(3), 135-148.
Xia, Y.; Kelton, C.M.L.; Guo, J.J.; Bian, B.; Heaton, P.C. Treatment of obesity: Pharmacotherapy trends in the united states from 1999 to 2010. Obesity , 2015, 23, 1721-1728.
Klonoff, D.C.; Greenway, F. Drugs in the pipeline for the obesity market. J. Diabetes Sci. Technol., 2008, 2, 913-918.
Hendricks, E.J. Off-Label drugs for weight management. Diabetes Metabol. Syndrome Obesity: Targets Therapy, 2017, 10, 223-234.
Aronne, L.; Shanahan, W.; Fain, R.; Glicklich, A.; Soliman, W.; Smith, S. Safety and efficacy of lorcaserin: A combined analysis of the BLOOM and BLOSSOM trials. Postgrad. Med., 2014, 126, 7-18.
Gurevich-panigrahi, T.; Panigrahi, S.; Wiechec, E.; Los, M. Obesity: Pathophysiology and clinical management. Curr. Med. Chem., 2009, 16(4), 506-521.
Adan, R.A.H. Mechanisms Underlying current and future anti-obesity drugs. Trends Neurosci., 2013, 36, 133-140.
Rodríguez, J.E. Past, present and future pharmacological therapy in obesity stimulants fat blockers antidepressants pharmacology treatment. Prim. Care Mar., , 2016, 43(1), 61-67.
Lois, K.; Kumar, S. Pharmacotherapy of Obesity. Endocrinol. Nutr., 2009, 56(4), 223-235.
Rodgers, R.J.; Tschop, M.H.; Wilding, J.P.H. Anti-Obesity drugs: Past, present and future. Dis. Model. Mech., 2012, 5, 621-626.
Hatahet, M.A.; Dhurandhar, N.V. Antiobesity drugs: Current and future issues. Curr. Diab. Rep., 2002, 2, 409-415.
Colman, E. Dinitrophenol and obesity: An early twentieth-century regulatory dilemma. Regul. Toxicol. Pharmacol., 2007, 48, 115-117.
Haslam, D. Weight Management In Obesity – Past and present. Int. J. Clin. Pract., 2016, 70(3), 206-217.
Hofbauer, E.; Karl, G.; Data, O.B. Pharmacotherapy of Obesity; CRC Press, 2004, Vol. 5, .
Hopkins, C.R. ACS chemical neuroscience molecule spotlight on lorcaserin. ACS Chem. Neurosci., 2010, 17(11), 718-719.
Smith, S.R.; Weissman, N.J.; Anderson, C.M.; Sanchez, M.; Chuang, E.; Stubbe, S.; Bays, H.; Shanahan, W.R. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med., 2010, 363.
Zhao, H.; Guo, Z. Medicinal chemistry strategies in follow-on drug discovery. Drug Discov. Today, 2009, 14, 516-522.
Redman, L.M.; Ravussin, E. Lorcaserin for the treatment of obesity. Drugs Today , 2010, 46, 901-910.
Hoy, S.M. Lorcaserin: A review of its use in chronic weight management. Drugs, 2013, 73, 463-473.
Smith, S.R.; Weissman, N.J.; Anderson, C.M.; Sanchez, M.; Chuang, E.; Stubbe, S.; Bays, H.; Shanahan, W.R. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) study group.Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med., 2010, 363, 245-256.
Harmonization, R.; Programme, M.; Issues, E. WHO Drug Information., 2012, 26.
Qihua Zhu; Wang, J.; Bian, X.; Zhang, L.; Wei, P.; Xu, Y. Novel synthesis of anti-obesity drug lorcaserin hydrochloride. Org. Process Res. Dev., 2015, 19, 1263-1267.
Cluzeau, J.; Stavber, G. Development and optimization of a new synthetic process for lorcaserin. Bioorg. Med. Chem., 2018, 26, 977-983.
Thomsen, W.J.; Grottick, A.J.; Menzaghi, F.; Reyes-saldana, H.; Espitia, S.; Yuskin, D.; Whelan, K.; Martin, M.; Morgan, M.; Chen, W.; Al-shamma, H.; Smith, B.; Chalmers, D.; Behan, D. Lorcaserin, a novel selective human 5-hydroxytryptamine 2c agonist: In Vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther., 2008, 325, 577-587.
Bajrai, A.A.; Ezzeldin, E.; Al-rashood, K.A.; Raish, M.; Iqbal, M. Article A validated UPLC – MS-MS assay for the rapid determination of lorcaserin in plasma and brain tissue samples. J. Anal. Toxicol., 2016, 40(2), 133-139.
Wani, D.V.; Rane, V.P.; Mokale, S.N. Liquid chromatographic separation and thermodynamic investigation of lorcaserin hydrochloride enantiomers on immobilized amylose-based chiral stationary phase. Chirality, 2018, 30, 284-292.
Rajput, S.J.; Sathe, M.A.; Patel, S.D. Development and validation of a hplc-based bioanalytical method for lorcaserin using solid phase extraction and application to a pharmacokinetic study in rats. Indian J. Pharm. Sci., 2018, 80, 235-241.
Hachem, R.; Malet-Martino, M.; Gilard, V. First identification and quantification of lorcaserin in an herbal slimming dietary supplement. J. Pharm. Biomed. Anal., 2014, 98, 94-99.
Bays, H.E. Lorcaserin: Drug profile and illustrative model of the regulatory challenges of weight-loss drug development. Expert Rev. Cardiovasc. Ther., 2011, 9, 265-277.
Fda Briefing Document Nda 200677 Pasireotide Injection: 600 Mcg, 900 Mcg Sponsor: Novartis Pharmaceuticals Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2012.
Colman, E. Department of health and human services public, health service food and drug administration center for drug evaluation and research., 2010, 1-11.
Smith, S.R.; Garvey, W.T.; Greenway, F.L.; Zhou, S.; Fain, R.; Pilson, R.; Fujioka, K.; Aronne, L.J. Coadministration of lorcaserin and phentermine for weight management: A 12-Week, randomized, pilot safety study. Obesity (Silver Spring), 2017, 25, 857-865.
For, A.; Disclosure, P.; Redaction, W. Lorcaserin hydrochloride briefing document for FDA advisory committee meeting., 2012.
Hurren, K.M.; Berlie, H.D. Lorcaserin: An Investigational Serotonin 2C Agonist for Weight Loss. Am. J. Heal. Pharm.,, 2011. 68, 2029 LP-2037.
Shukla, A.P.; Kumar, R.B.; Aronne, L.J. Lorcaserin Hcl for the Treatment of Obesity. Expert Opin. Pharmacother., 2015, 16, 2531-2538.
Sadeque, A.J.M.; Usmani, K.A.; Palamar, S.; Cerny, M.A.; Chen, W.G. Identification of Human UDP-Glucuronosyltransferases Involved in N-Carbamoyl Glucuronidation of Lorcaserin. Drug Metab. Dispos., 2012, 40, 772-778.
Sadeque, A.J.M.; Palamar, S.; Usmani, K.A.; Chen, C.; Cerny, M.A.; Chen, W.G. Identification of Human Sulfotransferases Involved in Lorcaserin N-Sulfamate Formation. Drug Metab. Dispos., 2016, 44, 570-575.
Berlie, H.D.; Hurren, K.M. Evaluation of Lorcaserin for the Treatment of Obesity. Expert Opin. Drug Metab. Toxicol., 2013, 9(8), 1053-1059.

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