Comparison of the Effects of Some Anorectic Drugs on Platelet and Brain 5-Hydroxy-Tryptamine (5 HT) in Rats

Abstract

A number of anorectic drugs have been studied for their effects on the uptake and release of 5 HT in platelets and on the levels of brain 5 HT and 5-hydroxyindolacetic acid (5HIAA) in the rat. Platelet studies have been performed in vitro, whereas brain levels have been measured after drug administration. Phentermine (α-dimethylphenylethylamine), die-thylpropion (2-diethylamino propiophenone) and d-amphetamine sulphate showed no effect on the above parameters. Mazindol (5(p-chlorophenyl)-2-5-dihydro-3H-imidazo-(2-1-α)isoindol-5-01) inhibited 5HT uptake by platelets, but neither induced release of 5HT from platelets nor modified 5HT or 5HIAA levels in the brain. Both d-fenfluramine H-Cl and 4-chloroamphetamine-HCl inhibited 5HT uptake by platelets, induced release of platelet-bound 5HT and lowered brain 5HT and 5HIAA levels. S 922 (trifluoro-methylphenyl(benzoyloxy)ethylamino-2-propane), a congener of fenfluramine, was inactive as an inhibitor of 5 HT uptake, was a weak releaser of 5 HT from platelets but effectively reduced 5HT and 5HIAA levels in the brain. This drug is rapidly metabolized in vivo to form fenfluramine.The in vivo effects of anorectic drugs on brain 5 HT levels seem therefore correlated with the capacity of these drugs to release in vitro 5 HT from platelets rather than with their in vitro inhibitory activity on platelet 5HT uptake.Supported by Grants 1ST. 73-00400-04 and H. 73-00218-31 of the Italian Research Council (C.N.R.).