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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Perspective

Lorcaserin: Worthy of Further Insights? Results from Recent Research

Author(s): Marianna Mazza*, Georgios D. Kotzalidis, Giuseppe Marano, Domenico De Berardis, Giovanni Martinotti, Enrico Romagnoli, Giuseppe Biondi-Zoccai, Antonio Abbate and Gabriele Sani

Volume 23, Issue 3, 2024

Published on: 28 April, 2023

Page: [278 - 283] Pages: 6

DOI: 10.2174/1871527322666230330124137

Price: $65

Abstract

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

« Previous Next »
[1]
De Deurwaerdère P, Ramos M, Bharatiya R, et al. Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats. Neuropharmacology 2020; 166: 107915.
[http://dx.doi.org/10.1016/j.neuropharm.2019.107915] [PMID: 31862271]
[2]
Halford JCG, Harrold JA. 5-HT(2C) receptor agonists and the control of appetite. Handb Exp Pharmacol 2012; 209(209): 349-56.
[http://dx.doi.org/10.1007/978-3-642-24716-3_16] [PMID: 22249823]
[3]
Smith BM, Smith JM, Tsai JH, et al. Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem 2008; 51(2): 305-13.
[http://dx.doi.org/10.1021/jm0709034] [PMID: 18095642]
[4]
Smith SR, Prosser WA, Donahue DJ, et al. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity 2009; 17(3): 494-503.
[http://dx.doi.org/10.1038/oby.2008.537]
[5]
Bays H, Perdomo C, Nikonova E, Knoth R, Malhotra M. Lorcaserin and metabolic disease: Weight‐loss dependent and independent effects. Obes Sci Pract 2018; 4(6): 499-505.
[http://dx.doi.org/10.1002/osp4.296] [PMID: 30574343]
[6]
Food and Drug Administration 2-13-2020 FDA Drug Safety Communication FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market Potential risk of cancer outweighs the benefits. Washington, D.C: Food and Drug Administration 2020.
[7]
Sharretts J, Galescu O, Gomatam S, Andraca-Carrera E, Hampp C, Yanoff L. Cancer risk associated with lorcaserin — The FDA’s Review of the CAMELLIA-TIMI 61 trial. N Engl J Med 2020; 383(11): 1000-2.
[http://dx.doi.org/10.1056/NEJMp2003873] [PMID: 32905671]
[8]
Extended Access Program With Lorcaserin For The Treatment of Dravet Syndrome and Other Refractory Epilepsies, NCT04457687, 2022. Available from: https://clinicaltrials.gov/ct2/show/NCT04457687?term=NCT04457687&draw=2&rank=1
[9]
Andrade ML, Fagundes PG, da Natividade RG, Frison SB, Colpani V, Gerchman F. Is lorcaserin really associated with increased risk of cancer? A systematic review and meta‐analysis. Obes Rev 2021; 22(3): e13170.
[http://dx.doi.org/10.1111/obr.13170] [PMID: 33258543]
[10]
Mathai ML. Has the bloom gone out of lorcaserin following the CAMELLIA-TIMI61 trial? Expert Opin Pharmacother 2021; 22(3): 261-4.
[http://dx.doi.org/10.1080/14656566.2020.1858795] [PMID: 33382010]
[11]
He Y, Liu H, Yin N, et al. Barbadin potentiates long-term effects of lorcaserin on pomc neurons and weight loss. J Neurosci 2021; 41(26): 5734-46.
[http://dx.doi.org/10.1523/JNEUROSCI.3210-20.2021] [PMID: 34031163]
[12]
Valenzuela-Vallejo L, Chrysafi P, Bello-Ramos J, Bsata S, Mantzoros CS. Circulating total and intact GDF-15 levels are not altered in response to weight loss induced by liraglutide or lorcaserin treatment in humans with obesity. Metabolism 2022; 133: 155237.
[http://dx.doi.org/10.1016/j.metabol.2022.155237] [PMID: 35700837]
[13]
Wagner S, Brierley DI, Leeson-Payne A, et al. Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression. Mol Metab 2023; 68: 101665.
[http://dx.doi.org/10.1016/j.molmet.2022.101665] [PMID: 36592795]
[14]
Neelakantan H, Holliday ED, Fox RG, et al. Lorcaserin suppresses oxycodone self-administration and relapse vulnerability in rats. ACS Chem Neurosci 2017; 8(5): 1065-73.
[http://dx.doi.org/10.1021/acschemneuro.6b00413] [PMID: 28107783]
[15]
Kohut SJ, Bergman J. Lorcaserin decreases the reinforcing effects of heroin, but not food, in rhesus monkeys. Eur J Pharmacol 2018; 840: 28-32.
[http://dx.doi.org/10.1016/j.ejphar.2018.09.025] [PMID: 30268662]
[16]
Levin FR, Mariani JJ, Pavlicova M, et al. Lorcaserin treatment for extended-release naltrexone induction and retention for opioid use disorder individuals: A pilot, placebo-controlled randomized trial. Drug Alcohol Depend 2021; 219: 108482.
[http://dx.doi.org/10.1016/j.drugalcdep.2020.108482] [PMID: 33418204]
[17]
Townsend EA, Negus SS, Poklis JL, Banks ML. Lorcaserin maintenance fails to attenuate heroin vs. food choice in rhesus monkeys. Drug Alcohol Depend 2020; 208: 107848.
[http://dx.doi.org/10.1016/j.drugalcdep.2020.107848] [PMID: 31982193]
[18]
Santos GM, Ikeda J, Coffin P, et al. Pilot study of extended-release lorcaserin for cocaine use disorder among men who have sex with men: A double-blind, placebo-controlled randomized trial. PLoS One 2021; 16(7): e0254724.
[http://dx.doi.org/10.1371/journal.pone.0254724] [PMID: 34265007]
[19]
Johns SE, Keyser-Marcus L, Abbate A, et al. Safety and preliminary efficacy of lorcaserin for cocaine use disorder: A phase I randomized clinical trial. Front Psychiatry 2021; 12: 666945.
[http://dx.doi.org/10.3389/fpsyt.2021.666945] [PMID: 34276440]
[20]
Grasing KW, Burnell K, De A. Biphasic reward effects are characteristic of both lorcaserin and drugs of abuse: Implications for treatment of substance use disorders. Behav Pharmacol 2022; 33(4): 238-48.
[http://dx.doi.org/10.1097/FBP.0000000000000672] [PMID: 35324488]
[21]
Arout CA, Cooper ZD, Reed SC, et al. 5HT‐2C agonist lorcaserin decreases cannabis self‐administration in daily cannabis smokers. Addict Biol 2021; 26(4): e12993.
[http://dx.doi.org/10.1111/adb.12993] [PMID: 33389797]
[22]
Brandt L, Jones JD, Martinez S, et al. Effects of lorcaserin on oxycodone self-administration and subjective responses in participants with opioid use disorder. Drug Alcohol Depend 2020; 208: 107859.
[http://dx.doi.org/10.1016/j.drugalcdep.2020.107859] [PMID: 31980285]
[23]
Levin ED, Johnson JE, Slade S, et al. Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats. J Pharmacol Exp Ther 2011; 338(3): 890-6.
[http://dx.doi.org/10.1124/jpet.111.183525] [PMID: 21636655]
[24]
DiPalma D, Rezvani AH, Willette B, et al. Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin. Pharmacol Biochem Behav 2019; 176: 16-22.
[http://dx.doi.org/10.1016/j.pbb.2018.11.002] [PMID: 30419272]
[25]
Fletcher PJ, Li Z, Silenieks LB, MacMillan C, DeLannoy I, Higgins GA. Preclinical evidence for combining the 5‐ HT 2C receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence. Addict Biol 2019; 24(3): 376-87.
[http://dx.doi.org/10.1111/adb.12602] [PMID: 29498158]
[26]
Zaniewska M, Nikiforuk A, Głowacka U, et al. Chronic lorcaserin treatment reverses the nicotine withdrawal-induced disruptions to behavior and maturation in developing neurons in the hippocampus of rats. Int J Mol Sci 2021; 22(2): 868.
[http://dx.doi.org/10.3390/ijms22020868] [PMID: 33467149]
[27]
Shanahan WR, Rose JE, Glicklich A, Stubbe S, Sanchez-Kam M. Lorcaserin for smoking cessation and associated weight gain: A randomized 12-week clinical trial. Nicotine Tob Res 2016; 19(8): ntw301.
[http://dx.doi.org/10.1093/ntr/ntw301] [PMID: 27815511]
[28]
Hurt RT, Croghan IT, Schroeder DR, Hays JT, Choi DS, Ebbert JO. Combination varenicline and lorcaserin for tobacco dependence treatment and weight gain prevention in overweight and obese smokers: A pilot study. Nicotine Tob Res 2016; 19(8): ntw304.
[http://dx.doi.org/10.1093/ntr/ntw304] [PMID: 27852796]
[29]
Hurt RT, Croghan IT, Schroeder DR, et al. Varenicline and lorcaserin for smoking cessation and weight gain prevention: A randomized clinical trial. Mayo Clin Proc Innov Qual Outcomes 2022; 6(5): 465-74.
[http://dx.doi.org/10.1016/j.mayocpiqo.2022.01.004] [PMID: 36160639]
[30]
Bohula EA, Wiviott SD, McGuire DK, et al. Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med 2018; 379(12): 1107-17.
[http://dx.doi.org/10.1056/NEJMoa1808721] [PMID: 30145941]
[31]
Pirtle JL, Hickman MD, Boinpelly VC, Surineni K, Thakur HK, Grasing KW. The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study. Pharmacol Biochem Behav 2019; 180: 52-9.
[http://dx.doi.org/10.1016/j.pbb.2019.02.010] [PMID: 30811963]
[32]
Shram MJ, Schoedel KA, Bartlett C, Shazer RL, Anderson CM, Sellers EM. Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users. Clin Pharmacol Ther 2011; 89(5): 683-92.
[http://dx.doi.org/10.1038/clpt.2011.20] [PMID: 21412231]
[33]
Negus SS, Banks ML. Learning from lorcaserin: Lessons from the negative clinical trial of lorcaserin to treat cocaine use disorder. Neuropsychopharmacology 2020; 45(12): 1967-73.
[http://dx.doi.org/10.1038/s41386-020-00815-4] [PMID: 32839526]
[34]
Anastasio NC, Sholler DJ, Fox RG, et al. Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration. Neuropharmacology 2020; 168: 108009.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108009] [PMID: 32145488]
[35]
Higgins GA, Fletcher PJ, Shanahan WR. Lorcaserin: A review of its preclinical and clinical pharmacology and therapeutic potential. Pharmacol Ther 2020; 205: 107417.
[http://dx.doi.org/10.1016/j.pharmthera.2019.107417] [PMID: 31629010]
[36]
Kapoor E, Faubion S, Hurt RT, et al. A selective serotonin receptor agonist for weight loss and management of menopausal vasomotor symptoms in overweight midlife women: A pilot study. Menopause 2020; 27(11): 1228-35.
[http://dx.doi.org/10.1097/GME.0000000000001599] [PMID: 33110038]

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