Diet-induced models of obesity (DIO) in rodents.

Obesity results from a complex interplay between a susceptible genotype and an environment that both promotes increased caloric intake and enables sustained decreases in energy expenditure. One commonly employed approach to modeling obesity in preclinical species is the diet-induced obese (DIO) rodent. Here, theoretical and practical considerations for producing obese rodents via dietary manipulation, and for assessing drug-induced changes in food intake and body weight are described.

Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia.

Insomnia affects a growing portion of the adult population in the U.S. Most current therapeutic approaches to insomnia primarily address sleep onset latency.

Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia.

5-Hydroxytryptamine (5-HT)(2A) receptor inverse agonists are promising therapeutic agents for the treatment of sleep maintenance insomnias. Among these agents is nelotanserin, a potent, selective 5-HT(2A) inverse agonist. Both radioligand binding and functional inositol phosphate accumulation assays suggest that nelotanserin has low nanomolar potency on the 5-HT(2A) receptor with at least 30- and 5000-fold selectivity compared with 5-HT(2C) and 5-HT(2B) receptors, respectively.