Effects of the alpha 2-adrenoceptor agonist guanfacine on growth and thermogenesis in mice

Guanfacine is an alpha 2-adrenoceptor agonist with antithermogenic properties. A single treatment of guanfacine caused a dose-related reduction in metabolic rate. The maximum reduction was 40%, and a dose of .5 mg/kg was close to that required to produce half this effect. It was determined whether the antithermogenic action of guanfacine would result in increased growth rate in mice. In animals treated once daily for 10 d (0, .125, .5, or 2 mg/kg), the drug caused dose-related reductions in feed intake, weight gain, and feed conversion efficiency. In a further experiment, mice were fed a restricted quantity of feed and treated for 14 d with guanfacine (.5 mg/kg twice daily). Because of repeated dosing, the antithermogenic effect of the drug was attenuated, so that metabolic rate was not lower in treated mice at the end of the experiment. Control and treated mice ate all the feed offered, but the guanfacine-treated group gained 2.9 g less weight (P < .01) than the controls. Half this difference in BW was accounted for by body water (P < .1), whereas body energy content was also reduced by the drug (P < .05). In a final experiment we sought possible sources of energy loss. Mice were treated with guanfacine (.5 mg/kg) three times over 24 h. Severe glucosuria was observed in the guanfacine-treated mice, with a tendency also toward increased output of fecal energy. We have confirmed that guanfacine has a powerful, if short-term, antithermogenic action. However, in mice, other effects of the drug on energy metabolism result in weight loss rather than growth stimulation.