The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Hideo Saji - One of the best experts on this subject based on the ideXlab platform.
-
Binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]Pyridinium Ion (HPP^+), a metabolite of haloperidol, to synthetic melanin: ImplicatIons for the dopaminergic neurotoxicity of HPP^+
Neurotoxicity Research, 2004Co-Authors: Hidekazu Kawashima, Yasuhiko Iida, Youji Kitamura, Hideo SajiAbstract:The toxicity of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]Pyridinium Ion (HPP^+), a metabolite of haloperidol, toward dopaminergic neurons was investigated. When HPP^+ (~100 µM) was added to primary cultures prepared from rat embryonic mesencephalon for 1 h, the survivability of dopaminergic neurons decreased significantly, and this effect was not inhibited by the dopamine transporter (DAT) inhibitor GBR 12909. In additIon, binding characteristics of HPP^+ to neuromelanin, which is abundant in dopaminergic neurons, was evaluated using synthetic melanin. A binding analysis using the Scatchard method showed that there are two classes of binding sites: high affinity sites with a dissociatIon constant K_d1 of 20.2 nM, and low affinity sites with a K_d2 of 4.0 µM. HPP^+ was released easily from synthetic melanin using phosphate buffer (pH 7.0), suggesting that this binding is reversible. The results suggest that the toxicity of HPP^+ in dopaminergic neurons is due not to DAT-mediated uptake, but to the binding to neuromelanin.
-
brain extractIon of 4 4 chlorophenyl 1 4 4 fluorophenyl 4 oxobutyl Pyridinium Ion hpp a neurotoxic metabolite of haloperidol studies using 3h hpp
Japanese Journal of Pharmacology, 2002Co-Authors: Hidekazu Kawashima, Yasuhiko Iida, Youji Kitamura, Yasushi Kiyono, Yasuhiro Magata, Hideo SajiAbstract: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.
Toshimitsu Okamura - One of the best experts on this subject based on the ideXlab platform.
-
an approach for measuring in vivo cerebral redox states using the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle
Free Radical Biology and Medicine, 2005Co-Authors: Toshimitsu Okamura, Tatsuya Kikuchi, Ayaka Nagamine, Kiyoshi Fukushi, Toshikazu Sekine, Yasushi Arano, Toshiaki IrieAbstract:This study was undertaken to develop radiopharmaceuticals for measuring in vivo cerebral redox states. Based on the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle, five N-[14C]methyl-3 or 3,5-substituted 1,4-dihydropyridines with different oxidatIon rates were designed, synthesized, and evaluated as a prototype of radiotracers for measuring in vivo cerebral redox states. When these tracers were injected into mice, they crossed the blood–brain barrier (BBB) and became trapped in the brain depending on their oxidatIon rates, while the corresponding oxidized forms hardly crossed the BBB. Furthermore, a significant increase in the radioactivity trapped in the brain was observed following injectIon of N-[14C]methyl-3-acetyl-1,4-dihydropyridine to mice pretreated with diethylmaleate that depletes glutathIone in the brain. These findings suggested that an approach based on the oxidative conversIon of dihydropyridine to the Pyridinium Ion and the metabolic trapping principle would be useful for measuring in vivo cerebral redox states.
-
original contributIon an approach for measuring in vivo cerebral redox states using the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle
2005Co-Authors: Toshimitsu Okamura, Tatsuya Kikuchi, Ayaka Nagamine, Kiyoshi Fukushi, Toshikazu Sekine, Yasushi Arano, Toshiaki IrieAbstract:This study was undertaken to develop radiopharmaceuticals for measuring in vivo cerebral redox states. Based on the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle, five N-[ 14 C]methyl-3 or 3,5-substituted 1,4dihydropyridines with different oxidatIon rates were designed, synthesized, and evaluated as a prototype of radiotracers for measuring in vivo cerebral redox states. When these tracers were injected into mice, they crossed the blood–brain barrier (BBB) and became trapped in the brain depending on their oxidatIon rates, while the corresponding oxidized forms hardly crossed the BBB. Furthermore, a significant increase in the radioactivity trapped in the brain was observed following injectIon of N-[ 14 C]methyl-3-acetyl-1,4-dihydropyridine to mice pretreated with diethylmaleate that depletes glutathIone in the brain. These findings suggested that an approach based on the oxidative conversIon of dihydropyridine to the Pyridinium Ion and the metabolic trapping principle would be useful for measuring in vivo cerebral redox states.
Hidekazu Kawashima - One of the best experts on this subject based on the ideXlab platform.
-
Binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]Pyridinium Ion (HPP^+), a metabolite of haloperidol, to synthetic melanin: ImplicatIons for the dopaminergic neurotoxicity of HPP^+
Neurotoxicity Research, 2004Co-Authors: Hidekazu Kawashima, Yasuhiko Iida, Youji Kitamura, Hideo SajiAbstract:The toxicity of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]Pyridinium Ion (HPP^+), a metabolite of haloperidol, toward dopaminergic neurons was investigated. When HPP^+ (~100 µM) was added to primary cultures prepared from rat embryonic mesencephalon for 1 h, the survivability of dopaminergic neurons decreased significantly, and this effect was not inhibited by the dopamine transporter (DAT) inhibitor GBR 12909. In additIon, binding characteristics of HPP^+ to neuromelanin, which is abundant in dopaminergic neurons, was evaluated using synthetic melanin. A binding analysis using the Scatchard method showed that there are two classes of binding sites: high affinity sites with a dissociatIon constant K_d1 of 20.2 nM, and low affinity sites with a K_d2 of 4.0 µM. HPP^+ was released easily from synthetic melanin using phosphate buffer (pH 7.0), suggesting that this binding is reversible. The results suggest that the toxicity of HPP^+ in dopaminergic neurons is due not to DAT-mediated uptake, but to the binding to neuromelanin.
-
brain extractIon of 4 4 chlorophenyl 1 4 4 fluorophenyl 4 oxobutyl Pyridinium Ion hpp a neurotoxic metabolite of haloperidol studies using 3h hpp
Japanese Journal of Pharmacology, 2002Co-Authors: Hidekazu Kawashima, Yasuhiko Iida, Youji Kitamura, Yasushi Kiyono, Yasuhiro Magata, Hideo SajiAbstract: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.
Toshiaki Irie - One of the best experts on this subject based on the ideXlab platform.
-
an approach for measuring in vivo cerebral redox states using the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle
Free Radical Biology and Medicine, 2005Co-Authors: Toshimitsu Okamura, Tatsuya Kikuchi, Ayaka Nagamine, Kiyoshi Fukushi, Toshikazu Sekine, Yasushi Arano, Toshiaki IrieAbstract:This study was undertaken to develop radiopharmaceuticals for measuring in vivo cerebral redox states. Based on the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle, five N-[14C]methyl-3 or 3,5-substituted 1,4-dihydropyridines with different oxidatIon rates were designed, synthesized, and evaluated as a prototype of radiotracers for measuring in vivo cerebral redox states. When these tracers were injected into mice, they crossed the blood–brain barrier (BBB) and became trapped in the brain depending on their oxidatIon rates, while the corresponding oxidized forms hardly crossed the BBB. Furthermore, a significant increase in the radioactivity trapped in the brain was observed following injectIon of N-[14C]methyl-3-acetyl-1,4-dihydropyridine to mice pretreated with diethylmaleate that depletes glutathIone in the brain. These findings suggested that an approach based on the oxidative conversIon of dihydropyridine to the Pyridinium Ion and the metabolic trapping principle would be useful for measuring in vivo cerebral redox states.
-
original contributIon an approach for measuring in vivo cerebral redox states using the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle
2005Co-Authors: Toshimitsu Okamura, Tatsuya Kikuchi, Ayaka Nagamine, Kiyoshi Fukushi, Toshikazu Sekine, Yasushi Arano, Toshiaki IrieAbstract:This study was undertaken to develop radiopharmaceuticals for measuring in vivo cerebral redox states. Based on the oxidative conversIon of dihydropyridine to Pyridinium Ion and the metabolic trapping principle, five N-[ 14 C]methyl-3 or 3,5-substituted 1,4dihydropyridines with different oxidatIon rates were designed, synthesized, and evaluated as a prototype of radiotracers for measuring in vivo cerebral redox states. When these tracers were injected into mice, they crossed the blood–brain barrier (BBB) and became trapped in the brain depending on their oxidatIon rates, while the corresponding oxidized forms hardly crossed the BBB. Furthermore, a significant increase in the radioactivity trapped in the brain was observed following injectIon of N-[ 14 C]methyl-3-acetyl-1,4-dihydropyridine to mice pretreated with diethylmaleate that depletes glutathIone in the brain. These findings suggested that an approach based on the oxidative conversIon of dihydropyridine to the Pyridinium Ion and the metabolic trapping principle would be useful for measuring in vivo cerebral redox states.
Jianjun Zhang - One of the best experts on this subject based on the ideXlab platform.
-
the novel squamosamide derivative compound flz attenuated 1 methyl 4 phenyl Pyridinium Ion mpp induced apoptosis and alternatIons of related signal transductIon in sh sy5y cells
Neuropharmacology, 2007Co-Authors: Dan Zhang, Jianjun ZhangAbstract:Abstract Compound FLZ (cFLZ) is a synthetic novel derivative of natural squamosamide. Previous pharmacological study found that cFLZ improved the abnormal behavior and the decrease of dopamine content in striatum in 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) model mice. 1-Methyl 4-phenylPyridinium (MPP+) is the active metabolite of MPTP to cause Parkinsonism in experimental animals. The purpose of this paper was to further study the protective actIon of cFLZ against MPP+-induced apoptosis and alternatIons of related signaling transductIon. The results indicated that cFLZ at concentratIons of 0.1 μM and 1 μM prevented 100 μM MPP+-induced apoptosis of SH-SY5Y cells, and inhibited the release of cytochrome C and apoptosis-inducing factor (AIF), and the activatIon of caspase 3 and NF-κB as well as α-synuclein gene and protein expressIons. The results suggest that cFLZ possesses potent neuroprotective activity and may be a potential anti-Parkinson's disease drug worthy for further study.
