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Brain distribution of geissoschizine methyl ether in rats using mass spectrometry imaging analysis.

Abstract
Geissoschizine methyl ether (GM) is one of the main active ingredients responsible for ameliorating the behavioral and psychological symptoms of dementia (BPSD) in Kampo medicine yokukansan. GM is mainly metabolized into hydroxylated forms (HM-1/2). However, the brain distributions of GM and HM has not been reported in vivo. In this study, therefore, the plasma concentrations and brain distribution of these compounds were examined in vivo using rats injected intravenously with GM. Plasma concentrations were analyzed using liquid chromatography-tandem mass spectrometry analysis and brain distribution using mass spectrometry imaging analysis. Plasma GM and HM-1 concentrations decreased in the 4 h after injection, whereas the concentration of plasma HM-2 increased at 4 h. In the 0.25 h-brain, GM signals were diffusely observed throughout the brain, including the cerebral cortex, hippocampus, striatum, thalamus, amygdala, cerebellum, and cerebral ventricle. HM signals were detected only in the ventricles of the brain at 4 h. These results suggest that plasma GM enters the brain and distributes in the parenchyma of various brain regions involved in BPSD, while plasma HM does not enter the brain parenchyma. This study is also the first to visually demonstrate the brain distribution of GM and its metabolite in vivo.
AuthorsTakashi Matsumoto, Yasushi Ikarashi, Mikina Takiyama, Junko Watanabe, Mitsutoshi Setou
JournalScientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 7293 (04 29 2020) ISSN: 2045-2322 [Electronic] England
PMID32350314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Indole Alkaloids
  • geissoschizine methylether
Topics
  • Animals
  • Brain (diagnostic imaging, metabolism)
  • Dementia (diagnostic imaging, drug therapy, metabolism)
  • Female
  • Indole Alkaloids (pharmacokinetics, pharmacology)
  • Mass Spectrometry
  • Rats
  • Rats, Wistar
  • Time Factors

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