Open AccessBrain Extraction of 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium Ion (HPP+), a Neurotoxic Metabolite of Haloperidol: Studies Using [3H]HPP+
Author(s) -
Hidekazu Kawashima,
Yasuhiko Iida,
Yoshihisa Kitamura,
Yasushi Kiyono,
Yasuhiro Magata,
Hideo Saji
Publication year - 2002
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.89.426
Subject(s) - haloperidol , pyridinium , chemistry , metabolite , dopaminergic , pharmacology , biochemistry , endocrinology , dopamine , medicine , medicinal chemistry
Tritium-labeled 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium ion (HPP+) was synthesized enzymatically from [3H]haloperidol using rat liver microsomal preparations, and using prepared [3H]HPP+, the passage of HPP+ into the brain was investigated. Consequently, HPP+ showed a moderate brain uptake index, indicating that it is able to permeate the blood-brain barrier. Furthermore, HPP+ was detected in murine brains after being intravenously injected. These results suggested that HPP+, produced mainly in the liver, is taken up into the brain and induces damage to brain dopaminergic neurons.