Tolerance pattern of the anorexigenic action of amphetamines, fenfluramine, phenmetrazine and diethylpropion in rats.

The tolerance pattern to anorectic drugs was studied in starved rats by measuring two consecutive 2 h food intakes. 2 There was a reduction in the first 2 h food intake with development of complete tolerance after fenfluramine and phenmetrazine, and of partial tolerance after amphetamine, (+)-amphetamine and diethylpropion. 3 During the second 2 h intake, the anorectic effect was transient after fenfluramine and diethylpropion; while there was an absolute increase in the intake after amphetamine and (+)-amphetamine. 4 A pair-feeding experiment revealed that the increase in the second 2 h food intake was not a direct effect of the drug but a consequence of the deficit in food intake during the preceding 2 hours. 5 There was an overall correlation between the food and water intake. 6 A significant loss in body weight was observed after amphetamine, fenfluramine and phenmetrazine but not after (+)-amphetamine or diethylpropion. 7 The results indicate that so-called tolerance to the anorexigenic effect of drugs is apparent rather than real and that the duration of food access is a determining factor. The body weight changes may be brought about by the metabolic effects of these drugs rather than their effect on food and water intake.