Brain Extraction of 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium Ion (HPP+), a Neurotoxic Metabolite of Haloperidol: Studies Using [3H]HPP+

Hidekazu Kawashima; Yasuhiko Iida; Youji Kitamura; Yasushi Kiyono; Yasuhiro Magata; Hideo Saji

doi:10.1254/jjp.89.426

Short Communications

Brain Extraction of 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium Ion (HPP⁺), a Neurotoxic Metabolite of Haloperidol: Studies Using [³H]HPP⁺

Hidekazu Kawashima, Yasuhiko Iida, Youji Kitamura, Yasushi Kiyono, Yasuhiro Magata, Hideo Saji

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Keywords: HPP⁺, Blood-brain barrier, Dopaminergic neuronal toxicity

JOURNAL FREE ACCESS

2002 Volume 89 Issue 4 Pages 426-428

DOI https://doi.org/10.1254/jjp.89.426

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Abstract

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.

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