AN AFFINITY-MODULATING SITE ON NEURONAL MONOAMINE TRANSPORT PROTEINS

The dissociation rates of [H-3]nisoxetine, [H-3]GBR 12935 and [H-3]cit alopram from, respectively, the rat brain noradrenaline, dopamine and 5-HT transporters were found to be markedly affected by several drugs. Sertraline strongly attenuated the rate of dissociation of [H-3]nisox etine from the noradrenaline transporter, while citaropram strongly at tenuated that of [H-3]citalopram from the 5-HT transporter. The effect s of both drugs were stereospecific. Less potent affinity-modulating d rugs were identified with regards to [H-3]GBR 12935 dissociation from the dopamine transporter. All three neuronal monoamine transporters ma y thus have specific affinity-modulating sites which change the functi on of the transporters with possible implications for the reuptake of monoamines released during synaptic activity.