Anticonvulsant action of ethanolamine-O-sulphate and di-n-propylacetate and the metabolism of γ-aminobutyric acid (GABA) in mice with audiogenic seizures
1976; Elsevier BV; Volume: 25; Issue: 4 Linguagem: Inglês
10.1016/0006-2952(76)90343-9
ISSN1873-2968
AutoresGill Anlezark, Roger W. Horton, B.S. Meldrum, Maria Christina, Bassel E. Sawaya,
Tópico(s)Advanced Chemical Sensor Technologies
ResumoMice susceptible to ‘audiogenic’ seizures (DBA/2, 21–25 days old) were treated with either di-n-propylacetate. DPA, (200–600 mg/kg, intraperitoneally) or ethanolamine-O-sulphate, EOS, (7.5–15 mg/kg, intracerebroventricularly). Motor behaviour was not moditied 45 min after DPA (except for slight changes after 600 mg/kg). Seizure responses to auditory stimulation were severely reduced after DPA 400 mg/kg, and totally absent after 600 mg/kg. Brain γ-aminobutyric acid (GABA) concentrations were unchanged after DPA 200–400 mg/kg, but increased by 57% after 600 mg/kg. The latter dose inhibited brain GABA-transaminase (4-aminobutyrate-2-oxoglutarate aminotransferase) activity by 33%. Kinetic studies with brain homogenates failed to show inhibition of GABA-transaminase activity by DPA (5–15 mM), but demonstrated inhibition of succinic Semialdehyde dehydrogenase by substrate competition. Mice tested 24 hr after EOS injection showed mild to moderate alaxia and were completely protected against ‘audiogenic’ seizures. Brain GABA concentration was increased 4–10 fold. GABA-transaminase activity was inhibited by 54–58% There was no inhibition of succinic Semialdehyde dehydrogenase activity.
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