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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.


K Murakami, H Yokoyama, K Onodera, K Iinuma, T Watanabe. AQ-0145, a newly developed histamine H3 antagonist, decreased seizure susceptibility of electrically induced convulsions in mice. Methods and findings in experimental and clinical pharmacology. 1995 Nov;17 Suppl C:70-3

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PMID: 8750799

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