Inano S
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
Yakubutsu Seishin Kodo. 1992 Aug;12(4):199-205.
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.
在小鼠中，静脉注射咖啡因（腺苷A1、A2受体拮抗剂）所诱发的强直性惊厥，可被L-PIA（腺苷A1受体激动剂）、NECA（腺苷A2受体激动剂）和2-ClAd（腺苷A1、A2受体激动剂）中的任何一种显著增强。咖啡因诱发的惊厥不受地西泮（苯二氮䓬受体激动剂）的影响，但被Ro 15-1788（拮抗剂或部分激动剂）抑制。β-DMCM（拮抗剂或反向激动剂）会增加惊厥。蝇蕈醇（GABA-a受体激动剂）、巴氯芬（GABA-b受体激动剂）和氨基氧乙酸（GABA转氨酶抑制剂）对咖啡因诱发的惊厥未显示出显著影响。荷包牡丹碱（GABA-a受体拮抗剂）和印防己毒素（氯离子通道阻滞剂）在不诱发惊厥的剂量下可显著增强惊厥。咖啡因诱发的惊厥可被非惊厥剂量的NMDA增强。CPP（竞争性NMDA受体拮抗剂）和MK-801（非竞争性NMDA受体拮抗剂）可显著抑制惊厥。这些结果表明，咖啡因诱发的惊厥不是由腺苷受体的阻断引起的。咖啡因可能作用于与GABA-a受体无联系的β-咔啉敏感苯二氮䓬受体（1型）。此外，这意味着咖啡因在NMDA受体钙离子通道复合物中发挥了某种作用。
