Phenethanolamine derivatives with calorigenic and antidiabetic qualities.

p-[(R)-3-[bis-[(R)-beta-hydroxyphenethyl]amino]butyl]benzamide (Ro 16-8714/000) is one of the most effective compounds, of a new series of calorigenic bis-phenethanolamine derivatives, which combine anti-obesity and antidiabetic qualities. Ro 16-8714 exhibited potent stimulation of oxygen consumption in normal rats and obese mice and rats. Calorigenesis appeared to be directly mediated by beta-adrenoceptors. Ro 16-8714 stimulated brown adipose tissue (BAT) thermogenesis in vitro and increased BAT calorigenic capacity in obese rodents during prolonged treatment. Furthermore, the compound induced fat mobilization and oxidation in normal and obese rats. Subchronic treatment of obese mice revealed potent antidiabetic effects which were mainly due to stimulation of carbohydrate oxidation. Prolonged treatment of obese mice and rats resulted in inhibition of body weight gain and depression of body fat content while body protein was maintained. The compound may, therefore, offer a new approach to the treatment of morbid obesity and maturity-onset diabetes.