title: [Obesity: a review of currently used antiobesity drugs and new compounds in clinical development].
abstract: This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).
authors.affiliation: Zakład Farmakodynamiki, Uniwersytet Medyczny w Łodzi, Łódź. remusz@wp.pl
authors.forename: Remigiusz
authors.initials: R
authors.lastname: Zieba
mesh_terms: D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003503:Cyclobutanes / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy*; D000077403:Orlistat; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D000077285:Rimonabant; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D007783:Lactones; D018377:Neurotransmitter Agents; D010880:Piperidines; D011720:Pyrazoles; D000077403:Orlistat; D000077285:Rimonabant; C058254:sibutramine