Investigational therapies in the treatment of obesity.
Obesity is a major public health concern and environmental factors are involved in its development. The hypothalamus is a primary site for the integration of signals for the regulation of energy homeostasis. Dysregulation of these pathways can lead to weight loss or gain. Some drugs in development can have favourable effects on body weight, acting on some of these pathways and leading to responses resulting in weight loss. Strategies for the management of weight reduction include exercise, diet, behavioural therapy, drug therapy and surgery. Investigational antiobesity medications can modulate energy homeostasis by stimulating catabolic or inhibiting anabolic pathways. Investigational drugs stimulating catabolic pathways consist of leptin, agonists of melanocortin receptor-4, 5-HT and dopamine; bupropion, growth hormone fragments, cholecystokinin subtype 1 receptor agonist, peptide YY3-36, oxyntomodulin, ciliary neurotrophic factor analogue, beta3-adrenergic receptor agonists, adiponectin derivatives and glucagon-like peptide-1. On the other hand, investigational drugs inhibiting anabolic pathways consist of the ghrelin receptor, neuropeptide Y receptor and melanin-concentrating hormone-1 antagonists; somatostatin analogues, peroxisome proliferator-activated receptor-gamma and -beta/delta antagonists, gastric emptying retardation agents, pancreatic lipase inhibitors, topiramate and cannabinoid-1 receptor antagonists. These differing approaches are reviewed and commented on in this article.
Mancini
Marcio C
MC
Sao Paulo University, Obesity & Metabolic Syndrome Group of the Endocrinology & Metabology Service, Faculty of Medicine, Hospital das Clínicas, Sao Paulo, Brazil. mmancini@usp.br
Halpern
Alfredo
A
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D015507:Drugs, Investigational / Q000494:pharmacology* / Q000627:therapeutic use; D004734:Energy Metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D054440:Receptors, Ghrelin; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use
D019440:Anti-Obesity Agents; D015507:Drugs, Investigational; D020738:Leptin; D047492:Peroxisome Proliferator-Activated Receptors; D044105:Receptor, Melanocortin, Type 4; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D017476:Receptors, Neuropeptide Y; D011994:Recombinant Proteins; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists