Development of anti-obesity agents: drugs that target neuropeptide and neurotransmitter systems.
BACKGROUND
Obesity results from an imbalance of energy intake and energy expenditure. While the prevalence of obesity is increasing and the negative impact on public health is being recognized, highly effective and safe therapy for obesity is not yet available.


OBJECTIVE
This review summarizes the current state of the art in the late-stage development area of anti-obesity drugs, provides a framework for understanding the potential disparity of animal data and human disease modification for some agents, and highlights novel agents that may provide significant clinical benefits in the future.


METHODS
Published literature and meeting proceedings were surveyed to review the late-stage development of new anti-obesity agents.


CONCLUSIONS
Most of the current clinical candidates for obesity treatment are targeting neurotransmitter receptors or peptide receptors. While new agents have been discovered, a significant failure rate also emerged. Rigorous scientific investigations, developing target engagement tools, and understanding any potential rodent versus human species difference will be necessary to ascertain mechanism-based efficacy and increase the probability of success.
Fong
Tung M
TM
Merck Research Laboratories, R80M-213, PO Box 2000, Rahway, NJ 07065, USA. tung_fong@merck.com
D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D019440:Anti-Obesity Agents; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter