Inhibition by β-carbolines of monoamine uptake into a synaptosomal preparation: Structure-activity relationships

The potency of a series of β-carboline compounds to inhibit ³H-serotonin (³H-5-HT) uptake into a synaptosomal suspension from mouse brain was studied. The $\text{in vitro}$ structure-activity study showed the tetrahydro-β-carbolines to be the most potent inhibitors compared to unsaturated β-carbolines. $\text{In vitro}$ inhibition of ³H-norepinephrine (³H-NE) and ³H-dopamine (³H-DA) uptake was determined for some tetrahydro-β-carbolines, and the degree of inhibition of uptake of these amines was less than that for ³H-5-HT (EC50s being 5–13 times those for ³H-5-HT). The tetrahydro-β-carbolines were also found to effectively inhibit ³H-5-HT but not ³H-NE or ³H-DA uptake when they were administered intra-peritoneally. These results suggest that the behavioral effects of the tetrahydro-β-carbolines which have been reported previously may be due to a relatively selective involvement of the serotonergic neurotransmitter system.