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

✍ Scribed by Paul Cumming; Albert Gjedde

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 1016 KB
• Volume: 15
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/syn.890150204

✦ Synopsis

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 ["Hlparoxetine in rat brain in vivo. Relative to [l4C1iodo-antipyrine, the brain uptake index (BUI) of r3H1paroxetine was 60-70%. The unidirectional blood clearance of [3H]paroxetine were 0.05-0.12 ml 8-l min-l, lower than expected from the BUI values. The steady state volume of distribution was 3.5 ml hg-I in the diencephalon and 1.8 ml g-l in the cerebellum, suggesting a binding potential of unity. Autoradiographs at four hours after [3Hlparoxetine injection (300 pCi, i.p.1 revealed heterogenous binding consistent with the calculated binding potentials. Binding was nearly absent from cerebellum and was highest in the dorsal raphe, 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 fluoxetine (10 mg/kg, i.p.1.