In vitro evidence for the presence of [3H]-haloperidol uptake in rat brain.
1 The neuroleptic [(3)H]-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) approximately equal to 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 [(3)H]-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 [(3)H]-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.
Ruiu
Stefania
S
Neuroscienze S.c.a.r.l., Via Palabanda 9, Cagliari 09123, Italy.
Marchese
Giorgio
G
Saba
Pier Luigi
PL
Satta
Rosalba
R
Gessa
GianLuigi
G
Vaccari
Andrea
A
Pani
Luca
L
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium / Q000378:metabolism*
D014316:Tritium; D006220:Haloperidol