In vitro evidence for the presence of [ 3H]-haloperidol uptake in rat brain

1. The neuroleptic [ 3H]-haloperidol (HP) was taken up in synaptosomes prepared from rat brain, in a temperature-, sodium ion-, and energy-dependent process. 2. The highest concentration of uptake sites (V max=2.37 pmol mg -1 protein min -1) was in the striatum with the other brain areas displaying lower (by 50-70%) values. 3. The affinity values (K m≈40 nM) were similar in all brain areas considered. 4. The pharmacological characterization did not indicate a well-defined group of inhibitors, which suggested that HP might not use a transporter for recognized neurotransmitters. 5. The HP metabolites tested, including HPTP, were competitive inhibitors of [ 3H]-HP uptake, an indirect indication that they may actively enter the striatal nerve endings through the same carrier. 6. Since the uptake process was partially affected by the incubation of [ 3H]-HP in the presence of several antagonists of HP-transforming cytochrome P450 isoforms, the binding of HP at some enzyme sites inside the synaptosome cannot be excluded. 7. In conclusion, the present results suggest that HP may be actively transported in the rat brain.