Ethacrynic acid-induced convulsions and brain neurotransmitters in mice.
Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50 micrograms/mouse) accelerated the synthesis/turnover of 5-hydroxytryptamine (5-HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in mouse brain. These effects were completely antagonized by pretreatment with a glutamate/N-methyl-D-aspartate antagonist, aminophosphonovaleric acid. In ethacrynic acid-induced convulsions, these neurotransmitter systems may be differentially modulated, probably through activation of glutaminergic neurons in the brain.
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
M
M
Inoue
T
T
Hirose
T
T
Yasukura
C
C
Inagaki
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018118:Chloride Channels; D004976:Ethacrynic Acid / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D051379:Mice; D017470:Receptors, Glutamate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018118:Chloride Channels; D008565:Membrane Proteins; D017470:Receptors, Glutamate; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D004976:Ethacrynic Acid; D000109:Acetylcholine