ICI D7114: a novel selective adrenoceptor agonist of brown fat and thermogenesis.
Increasing energy expenditure by treatment with thermogenic drugs is not new, but available drugs have suffered from the problem of lack of selectivity. In the last decade two key findings have allowed the development of selective thermogenic drugs that have promise in the treatment of obesity. 1) The recognition that brown adipose tissue (BAT) plays a role in compensatory increases in energy expenditure has allowed an approach directed at a target organ. 2) The demonstration showing that increases in the activity of BAT may be modulated by an atypical (beta 3) adrenoceptor has led to the development of a new peripherally acting beta-adrenoceptor agonist ICI D7114, which stimulates thermogenesis at doses that have little effect on beta 1 or beta 2 adrenoceptors. Treatment with the compound activates BAT and thermogenesis even in species and situations where the intrinsic capacity is low. 3) The compound has beneficial effects in animal models of obesity and disturbed glucose and lipid homeostasis.
ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
B R
BR
Holloway
R
R
Howe
B S
BS
Rao
D
D
Stribling
D002001:Adipose Tissue, Brown / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D010642:Phenoxyacetates / Q000494:pharmacology* / Q000627:therapeutic use; D050198:Phenoxypropanolamines
D000318:Adrenergic beta-Agonists; D010642:Phenoxyacetates; D050198:Phenoxypropanolamines; C071909:ICI D7114