In Vivo Distribution of CGS‐19755 Within Brain in a Model of Focal Cerebral Ischemia

Matthew J. Hogan, Albert Gjedde, Antoine M. Hakim

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: The blood–brain barrier permeability of the competitive N‐methyl‐D‐aspartate receptor antagonist CGS‐19755 [cis‐4‐(phosphonomethyl)‐2‐piperidine carboxylic acid] was assessed in normal and ischemic rat brain. The brain uptake index of CGS‐19755 relative to iodoantipyrine was assessed using the Oldendorf technique in normal brain. The average brain uptake index in brain regions supplied by the middle cerebral artery was 0.15 ± 0.35% (mean ± SEM). The unidirectional clearance of CGS‐19755 from plasma across the blood–brain barrier was determined from measurements of the volume of distribution of CGS‐19755 in brain. These studies were performed in normal rats and in rats with focal cerebral ischemia produced by combined occlusion of the proximal middle cerebral artery and ipsilateral common carotid artery. In normal rats the regional plasma clearance across the blood–brain barrier was low, averaging 0.015 ml 100 g−1 min−1. In ischemic rats this clearance value averaged 0.019 ml 100 g−1 min−1 in the ischemic hemisphere and 0.009 ml 100 g−1 min−1 in the nonischemic hemisphere. No significant regional differences in plasma clearance of CGS‐19755 were observed in either normal or ischemic rats except in cortex injured by electrocautery where a 14‐fold increase in clearance across the blood–brain barrier was measured. We conclude that CGS‐19755 crosses the blood–brain barrier very slowly, even in acutely ischemic tissue.

Original languageEnglish (US)
Pages (from-to)186-191
Number of pages6
JournalJournal of Neurochemistry
Volume58
Issue number1
DOIs
StatePublished - Jan 1992

Keywords

  • Blood–brain barrier permeability
  • CGS‐19755
  • Competitive N‐methyl‐D‐aspartate antagonists
  • Focal cerebral ischemia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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