Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice.

Abstract

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.

• Authors: G J Amabeoku
• Journal: General pharmacology (Gen Pharmacol) Vol. 32 Issue 3 Pg. 365-72 (Mar 1999) ISSN: 0306-3623 [Print] England
• PMID: 10211593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminobutyrates
• GABA Agonists
• GABA Antagonists
• Receptors, GABA
• Receptors, Glutamate
• Picrotoxin
• Aminooxyacetic Acid
• Muscimol
• 2,4-diaminobutyric acid
• gamma-Aminobutyric Acid
• N-Methylaspartate
• Ketamine
• Dextromethorphan
• 2-Amino-5-phosphonovalerate
• Theophylline
• N-methyl-DL-aspartic acid
• Baclofen
• Clonidine
• Bicuculline

Topics

• 2-Amino-5-phosphonovalerate (pharmacology)
• Aminobutyrates (pharmacology)
• Aminooxyacetic Acid (pharmacology)
• Animals
• Baclofen (pharmacology)
• Bicuculline (pharmacology)
• Clonidine (pharmacology)
• Dextromethorphan (pharmacology)
• Drug Interactions
• Female
• GABA Agonists (pharmacology)
• GABA Antagonists (pharmacology)
• Ketamine (pharmacology)
• Mice
• Muscimol (pharmacology)
• N-Methylaspartate (analogs & derivatives, pharmacology)
• Picrotoxin (pharmacology)
• Receptors, GABA (drug effects, metabolism)
• Receptors, Glutamate (drug effects, metabolism)
• Seizures (chemically induced, metabolism)
• Theophylline (toxicity)
• gamma-Aminobutyric Acid (metabolism)