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

Abstract

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.

• Authors: S Inano
• Journal: Yakubutsu, seishin, kodo = Japanese journal of psychopharmacology (Yakubutsu Seishin Kodo) Vol. 12 Issue 4 Pg. 199-205 (Aug 1992) ISSN: 0285-5313 [Print] Japan
• PMID: 1329401 (Publication Type: English Abstract, Journal Article)

Chemical References

• Receptors, GABA-A
• Receptors, N-Methyl-D-Aspartate
• Receptors, Purinergic
• Benzodiazepines
• Muscimol
• Caffeine
• Flumazenil
• Dizocilpine Maleate
• Baclofen
• Diazepam

Topics

• Animals
• Baclofen (pharmacology)
• Benzodiazepines (antagonists & inhibitors, pharmacology)
• 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)