Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice.
The effects of drugs affecting GABA and glutamic acid receptors on theophylline-induced seizures were investigated in mice. Theophylline elicited tonic seizures in mice in a dose dependent manner. Muscimol, DABA and AOAA significantly prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. Baclofen significantly delayed the onset of the tonic seizures induced by theophylline. Bicuculline and picrotoxin significantly shortened the onset and significantly increased the incidence of seizures induced by a low dose of theophylline and also significantly antagonized muscimol-attenuating effect against theophylline seizures. N-methyl-DL-aspartic acid significantly shortened the onset and significantly increased the incidence of seizures elicited by a low dose of theophylline. D-(-)-2-amino-phosphonopentanoic acid effectively delayed the onset and significantly decreased the incidence of seizures elicited by theophylline and also significantly antagonized the potentiating effect of N-methyl-DL-aspartic acid on seizures induced by a low dose of theophylline. Dextromethorphan and ketamine profoundly shortened the onset of theophylline-induced seizures. Clonidine effectively prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. These data indicate that GABA(A) and N-methyl-D-aspartic acid receptors may mediate theophylline-elicited tonic seizures in mice.
Amabeoku
G J
GJ
Department of Pharmacology, School of Pharmacy, University of the Western Cape, Bellville, South Africa. george@pharmacy.uwc.ac.2a
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000031:analogs & derivatives / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D013806:Theophylline / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015763:2-Amino-5-phosphonovalerate; D000613:Aminobutyrates; D000625:Aminooxyacetic Acid; D001418:Baclofen; D001640:Bicuculline; D003000:Clonidine; D003915:Dextromethorphan; D018755:GABA Agonists; D018756:GABA Antagonists; D007649:Ketamine; D009118:Muscimol; D016202:N-Methylaspartate; D010852:Picrotoxin; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D013806:Theophylline; D005680:gamma-Aminobutyric Acid; C005959:2,4-diaminobutyric acid; C083705:N-methyl-DL-aspartic acid