Cefoselis, a β-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release

K. Ohtaki, K. Matsubara, S. Fujimaru, K. Shimizu, T. Awaya, Manabu Suno, K. Chiba, N. Hayase, H. Shiono

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cefoselis is a widely used β-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, β-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in γ-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

Original languageEnglish
Pages (from-to)1523-1535
Number of pages13
JournalJournal of Neural Transmission
Volume111
Issue number12
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Fingerprint

Lactams
Blood-Brain Barrier
Glutamic Acid
Seizures
Anti-Bacterial Agents
Renal Insufficiency
Extracellular Fluid
Brain
Microdialysis
gamma-Aminobutyric Acid
Hippocampus
cefoselis
Aminobutyrates
Cefazolin
GABA Receptors
Cephalosporins
Intravenous Injections
Tail
Veins
Kidney

Keywords

  • γ-aminobutyric acid
  • Blood-brain barrier
  • Cefazolin
  • Cefoselis
  • Excitatory amino acid
  • Glutamate
  • Microdialysis
  • Renal failure

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cefoselis, a β-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release. / Ohtaki, K.; Matsubara, K.; Fujimaru, S.; Shimizu, K.; Awaya, T.; Suno, Manabu; Chiba, K.; Hayase, N.; Shiono, H.

In: Journal of Neural Transmission, Vol. 111, No. 12, 12.2004, p. 1523-1535.

Research output: Contribution to journalArticle

Ohtaki, K. ; Matsubara, K. ; Fujimaru, S. ; Shimizu, K. ; Awaya, T. ; Suno, Manabu ; Chiba, K. ; Hayase, N. ; Shiono, H. / Cefoselis, a β-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release. In: Journal of Neural Transmission. 2004 ; Vol. 111, No. 12. pp. 1523-1535.
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