An affinity-modulating site on neuronal monoamine transport proteins.

The dissociation rates of [H-3]nisoxetine, [H-3]GBR 12935 and [H-3]citalopram 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]nisoxetine from the noradrenaline transporter, while citaropram strongly attenuated that of [H-3]citalopram from the 5-HT transporter. The effects of both drugs were stereospecific. Less potent affinity-modulating drugs were identified with regards to [H-3]GBR 12935 dissociation from the dopamine transporter. All three neuronal monoamine transporters may thus have specific affinity-modulating sites which change the function of the transporters with possible implications for the reuptake of monoamines released during synaptic activity.