Tolerance and cross tolerance to the anorexigenic effect of appetite suppressants in rats.

Rats were treated chronically with various anorexigenic substances which were administered orally once (or twice) daily or bidaily. Complete tolerance to the anorectic effect of d-amphetamine, fenfluramine, benfluorex (780 SE), chlorphentermine, and mazindol developed in 11-17 days. Test doses were given at different points of time after withdrawal in order to recognize the presence or absence of direct or cross tolerance. Direct tolerance to fenfluramine and benfluorex persisted for 46 days, whereas tolerance to mazindol was no longer present at day 20. There was lasting bidirectional cross tolerance between chlorphentermine and fenfluramine, transient bidirectional cross tolerance between mazindol and amphetamine, but only unidirectional cross tolerance between amphetamine and fenfluramine.