Effect of mazindol, d-amphetamine and diethylpropion on purine nucleotide binding to brown adipose tissue

Amphetamine, diethylpropion and mazindol were administered to rats in both acute and chronic experiments to measure the changes in purine nucleotide (GDP) binding to the mitochondria from interscapular brown adipose tissue. There was a dose-dependent response to acute treatment with mazindol, but no such effect with diethylpropion. The effects of mazindol and amphetamine were present as early as 3 hours after treatment, and persisted for at least 48 hours, when compared to vehicle-injected rats when all rats were fasted from the time of injection until study. There was no effect when these drugs were added in vitro to mitochondria from brown adipose tissue. Diethylpropion had no effect on GDP binding either in vivo or in vitro at any of the times tested. Following 11 days of treatment with diethylpropion, amphetamine or mazindol, there was a significant increase in purine nucleotide (GDP) binding to mitochondria only in the amphetamine-treated animals. There was no difference in body weight or food intake with any of the three drugs after the third day of chronic treatment. The differences between the effects of these three drugs and those of fenfluramine are discussed in terms of their different central mechanisms of action.