Ephedrine, a potential slimming drug, directly stimulates thermogenesis in brown adipocytes via beta-adrenoreceptors.

Ephedrine is a potential slimming drug that stimulates thermogenesis in man and laboratory animals. Considering that brown adipose tissue is an important site of catecholamine-induced thermogenesis in homeotherms, we tested the thermogenic efficiency of several ephedrine stereoisomers on adipocytes isolated from rat interscapular brown adipose tissue. Addition of (-)-ephedrine (0.1 mM) to brown adipocyte suspensions rapidly stimulated cellular respiration eight times above basal values. A stable Vmax of 335 nmol O2/min/10(6) cells was reached less than 5 min after the onset of respiratory stimulation. This value represents 85 percent of the maximal respiration observed with norepinephrine, the physiological effector of thermogenesis. The (-)isomer of ephedrine (1/2 Vmax = 20 microM) was more potent that other stereoisomers (+)-psi-ephedrine, (-)-psi-ephedrine (racephedrine) in enhancing brown adipocyte respiration. Beta-Adrenergic antagonists (alprenolol and propranolol) were much more effective than alpha-adrenergic antagonists (phentolamine and phenoxybenzamine) in inhibiting the respiratory effects of ephedrine. It is concluded that (-)-ephedrine mimics the calorigenic action of norepinephrine by directly stimulating brown adipocyte respiration via beta-adrenoreceptors.