Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate.
The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.
D000161:Acoustic Stimulation; D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D011339:Probenecid / Q000494:pharmacology; D014631:Valerates / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D000927:Anticonvulsants; D001679:Biogenic Amines; D004983:Ethanolamines; D008781:Methyltyrosines; D014631:Valerates; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D011339:Probenecid; D010134:Fenclonine