Fat-mobilizing action of amphetamine

The effects of amphetamine and methamphetamine on plasma free fatty acid (FFA), blood glucose, serum total fat, and triglyceride concentrations were investigated in 21 subjects; the effect of epinephrine were studied in an identical manner in 14 subjects. The administration of amphetamine and methamphetamine led to an increase in the plasma FFA concentration. No significant changes were found in the blood glucose, serum total fat, and triglyceride concentrations. Kinetic studies of FFA were also made in some of the subjects receiving amphetamine, methamphetamine, and epinephrine. It was shown that amphetamine and methamphetamine lead to an augmentation of plasma FFA pool due to a primary increase of FFA production rate. Catecholamine depletion, by prolonged parenteral adminstration of reserpine, nearly completely abolished the adipokinetic action of amphetamine whereas the effect of epinephrine was greatly potentiated. This was interpreted as evidence for the dependence of the adipokinetic action of amphetamine on endogenous catecholamines. ESTIMATED FROM A DOSE RATIO (AMPHETAMINE: epinephrine) of 352:1, the relative adipokinetic potency of amphetamine, expressed as peak DeltaFFA rise, +DeltaFFA area, and DeltaFFA production rate, respectively, was found to be 55, 84, and 39% in comparison with the same effects of epinephrine. The more pronounced changes in +DeltaFFA area reflect the longer duration of action of amphetamine viz. epinephrine. This study demonstrates that amphetamine is an adipokinetic agent causing an increase in the plasma FFA pool of a lesser extent but of longer duration than equipressor doses of epinephrine. The mechanism of fat-mobilizing action of amphetamine is indirect i.e., dependent on endogenous catecholamine release.