Yokoyama H, Onodera K, Iinuma K, Watanabe T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Pharmacol Biochem Behav. 1994 Mar;47(3):503-7. doi: 10.1016/0091-3057(94)90151-1.
The effects of intracerebroventricular (ICV) administration of histamine and its selective agonists on electrically and pentylenetetrazole-induced convulsions in mice were studied. The ICV administration of histamine decreased seizure susceptibility on electrically and pentylenetetrazole-induced convulsions significantly and dose-dependently. The inhibitory effects of histamine were well antagonized by centrally acting histamine H1 antagonists such as pyrilamine (or mepyramine) and ketotifen, but not by a peripherally acting histamine H1 antagonist, astemizole, or a centrally acting H2 antagonist, zolantidine. The ICV administration of 2-thiazolylethylamine, a selective histamine H1 agonist, also decreased seizure susceptibility, which could be antagonized by centrally acting histamine H1 antagonists, whereas dimaprit, a selective histamine H2 agonist, did not affect seizure susceptibility. These findings strengthened the idea that the central histaminergic neuron system plays an inhibitory role in convulsions.
研究了脑室内（ICV）注射组胺及其选择性激动剂对小鼠电刺激和戊四氮诱导惊厥的影响。脑室内注射组胺可显著且剂量依赖性地降低电刺激和戊四氮诱导惊厥的易感性。组胺的抑制作用可被中枢作用的组胺H1拮抗剂如吡苄明（或美吡拉敏）和酮替芬很好地拮抗，但不能被外周作用的组胺H1拮抗剂阿司咪唑或中枢作用的H2拮抗剂佐兰丁拮抗。脑室内注射选择性组胺H1激动剂2-噻唑基乙胺也可降低惊厥易感性，这可被中枢作用的组胺H1拮抗剂拮抗，而选择性组胺H2激动剂二甲双胍对惊厥易感性没有影响。这些发现强化了中枢组胺能神经元系统在惊厥中起抑制作用的观点。
