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Centrally Acting Agents for Obesity: Past, Present, and Future.
Drugs. 2018 Jul; 78(11):1113-1132.D

Abstract

For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues.

Authors+Show Affiliations

Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA.Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA.Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA. Frank.Greenway@pbrc.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30014268

Citation

Coulter, Ann A., et al. "Centrally Acting Agents for Obesity: Past, Present, and Future." Drugs, vol. 78, no. 11, 2018, pp. 1113-1132.
Coulter AA, Rebello CJ, Greenway FL. Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs. 2018;78(11):1113-1132.
Coulter, A. A., Rebello, C. J., & Greenway, F. L. (2018). Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs, 78(11), 1113-1132. https://doi.org/10.1007/s40265-018-0946-y
Coulter AA, Rebello CJ, Greenway FL. Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs. 2018;78(11):1113-1132. PubMed PMID: 30014268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Centrally Acting Agents for Obesity: Past, Present, and Future. AU - Coulter,Ann A, AU - Rebello,Candida J, AU - Greenway,Frank L, PY - 2018/7/18/pubmed PY - 2019/5/17/medline PY - 2018/7/18/entrez SP - 1113 EP - 1132 JF - Drugs JO - Drugs VL - 78 IS - 11 N2 - For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues. SN - 1179-1950 UR - https://www.unboundmedicine.com/medline/citation/30014268/Centrally_Acting_Agents_for_Obesity:_Past_Present_and_Future_ L2 - https://dx.doi.org/10.1007/s40265-018-0946-y DB - PRIME DP - Unbound Medicine ER -