Beta3-adrenergic agonists: potential therapeutics for obesity.
During the last decade a number of beta3-adrenergic receptor agonists have been advanced to clinical trials. The results of human studies to date have been disappointing with respect to sustained increases in metabolic rate and weight loss. Cloning of beta3-adrenoceptors in a number of species and subsequent pharmacological evaluations revealed these early investigational drugs to be weakly active against the human receptor, suggesting an explanation for the poor performance of these compounds in clinical trials. This information has been integrated into subsequent research efforts resulting in the discovery of agents with activities optimised for the human receptor. This new generation of compounds is in late preclinical/early clinical development and are poised to address the role beta3-adrenoceptor signalling plays in the obese state. Issues related to the potential for beta3-adrenergic agonists to positively impact metabolic parameters in humans are also discussed.
Central Research Division, Pfizer, Inc., Eastern Point Road, Groton, CT 06340, USA.
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