Abstract

Fenfluramine and amphetamine both inhibit the accumulation of ³H-norepinephrine into rat brain cortex tissue slices but d-amphetamine is about 50 times more potent than either d-, l- or dl-fenfluramine. When ³H-norepinephrine is added to cortex slices in the presence of fenfluramine, oxidative deamination of ³H-norepinephrine is reduced markedly. This effect is similar to that observed with d-amphetamine and it is suggested that it is due to inhibition of neuronal uptake, thus limiting access of norepinephrine to intraneuronal monoamine oxidase. When tissues are incubated with ³H-norepinephrine prior to exposure to the drugs, both fenfluramine and amphetamine release ³H-norepinepimrine into the media; fenfluramine is again less potent than amphetamine. Under these conditions, fenfluramime increases the amount of ³H-deaminated metabolites which are formed. This is in contrast to amphetamine which either causes no change or decreases the amount of ³H-deaminated metabolites. If the tissue is exposed to pargyline, a monoamine oxidase inhibitor, the amount of ³H-norepinephrine released into the media by fenfluramine is increased markedly when compared to the amount released by fenfluramine alone. After pargyline treatment, fenfluramine is equipoteat with amphetamine. The effect of amphetamine on the release of norepinephrine is not increased significantly by treatment with pargyline. These results suggest that fenfluramine and amphetamine differ in the mechanism by which they release norepinephrine from brain tissue. Amphetamime releases unmetabolized norepinephrine, whereas fenfluramine releases norepinephrine in such a manner that it has increased access to monoamine oxidase.