Murakami K, Yokoyama H, Onodera K, Iinuma K, Watanabe T
The Green Cross Corporation, Osaka, Japan.
Methods Find Exp Clin Pharmacol. 1995 Nov;17 Suppl C:70-3.
We studied the effect of AQ-0145, a newly developed histamine H3-receptor antagonist, on electrically induced convulsions in mice. AQ-0145 significantly decreased the durations of each convulsive phase. The anticonvulsant effect of AQ-0145 was antagonized by mepyramine (pyrilamine) and ketotifen, centrally acting histamine H1-receptor antagonists. Thus, the blockade by histamine H1 antagonists of the AQ-0145-induced decrease in seizure susceptibility indicated that histamine released by AQ-0145 from the histaminergic nerve terminals interacts with the histamine H1 receptors of postsynaptic neurons. These findings fully support the hypothesis that the central histaminergic neuronal system is involved in the inhibition of seizures. It is suggested that the neuropharmacological data on histamine H3 ligands may provide clinical candidates for the CNS disorders in which histamine plays important roles in mental and behavioral functions. In this study, it was suggested that AQ-0145 was a new clinical candidate of H3 ligands.
我们研究了新开发的组胺H3受体拮抗剂AQ - 0145对小鼠电惊厥的影响。AQ - 0145显著缩短了各惊厥阶段的持续时间。中枢性组胺H1受体拮抗剂美吡拉敏（吡苄明）和酮替芬可拮抗AQ - 0145的抗惊厥作用。因此，组胺H1拮抗剂对AQ - 0145诱导的癫痫易感性降低的阻断作用表明，AQ - 0145从组胺能神经末梢释放的组胺与突触后神经元的组胺H1受体相互作用。这些发现充分支持了中枢组胺能神经系统参与癫痫抑制的假说。提示关于组胺H3配体的神经药理学数据可能为组胺在精神和行为功能中起重要作用的中枢神经系统疾病提供临床候选药物。在本研究中，提示AQ - 0145是H3配体的一种新的临床候选药物。
