Kinetics of the uptake of [³H]paroxetine in the rat brain

Paroxetine, an antidepressant with a high affinity for serotonin (5‐HT) re‐uptake sites, is a potential tracer of these sites. We determined the kinetic properties of [³H]paroxetine in rat brain in vivo. Relative to [¹⁴C]iodo‐antipyrine, the brain uptake index (BUI) of [³H]paroxetine was 60–70%. The unidirectional blood clearance of [³H]paroxetine were 0.05–0.12 ml g⁻¹ min⁻¹, lower than expected from the BUI values. The steady state volume of distribution was 3.5 ml hg⁻¹ in the diencephalon and 1.8 ml ⁻¹ in the cerebellum, suggesting a binding potential of unity. Autoradiographs at four hours after [³H] paroxetine injection (300 μCi, i.p.) revealed heterogenous binding consistent with the calculated binding potentials. Binding was nearly absent from cerebellum and was highest in the dorsal raphé, superior colliculus, dorsal hypothalamus, and entorhinal cortex, but did not reach equilibrium in four hours of tracer circulation. The specific binding relative to vermis was displaced by pretreatment with fluonotino (10 mg/kg, i.p.). © 1993 Wiley‐Liss. Inc.