[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice].

Article date: 1992/8/1

PubMed ID: 1329401

Journal name: Yakubutsu, seishin, kodo = Japanese journal of psychopharmacology (ISSN: 0285-5313)


In mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.

Author List: Inano S

Publication Types: English Abstract; Journal Article

Substances mentioned in the article: Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic; Benzodiazepines; Muscimol; Caffeine; Flumazenil; Dizocilpine Maleate; Baclofen; Diazepam;

Mesh terms: Animals; Baclofen/pharmacology; Benzodiazepines/antagonists & inhibitors; Caffeine/toxicity; Diazepam/pharmacology; Dizocilpine Maleate/pharmacology; Flumazenil/pharmacology; Male; Mice; Muscimol/pharmacology; Receptors, GABA-A/drug effects; Receptors, N-Methyl-D-Aspartate/drug effects; Receptors, Purinergic/drug effects; Seizures/chemically induced;

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