Characterization of high affinity and stereospecific [ (3)H ]d- fenfluramine binding to rat brain

Specific binding of [(3)H]d- fenfluramine , an anorectic agent acting on serotonergic system, was characterized in rat total brain minus cerebellum. The binding was reversible, stereospecific and with high affinity (K(d) about 80 nM). The receptor density in total brain was about 32 pmol/g tissue. Subcellular distribution showed a preferential localization in the microsomal and membrane fractions. The pharmacological characterization of [(3)H]d- fenfluramine specific binding showed that the d-normetabolite and the serotonin-uptake inhibitors are the most active compounds; d-amphetamine was inactive in inhibiting [(3)H]d- fenfluramine binding; NaC1 and GTP decreased [(3)H]d- fenfluramine binding. Although the results are not fully conclusive in clarifying the meaning of [(3)H]d- fenfluramine binding to rat brain membranes, the implication of these sites in mediating the anorectic activity of the drug is proposed.