| Co-Investigator(Kenkyū-buntansha) |
MEGURO Ken-ichi Tohoku Univ., Sch. of Med. Assist. Pro, 医学部, 助手 (90239559)
YANAI Kazuhiko Tohoku Univ, Sch. of Med. Assoc. Pro, 医学部, 助教授 (50192787)
ICHINOSE Masakazu Tohoku Univ., Sch. of Med. Assist. Pro, 医学部, 助手 (80223105)
ONODERA Kenji Tohoku Univ., Sch. of Dent. Lecturer, 歯学部, 講師 (40133988)
MAEYAMA Kazutama Ehime Univ., Sch. of Med. Prof., 医学部, 教授 (00157158)
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| Research Abstract |
Histamine H3 receptor is a presynaptic autoreceptor of the central histaminegic neuron system and regulates the synthesis and release of hitamine. Recently, H3 receptor was found to locate in the periphery and other neuron systems. In this recearch, we examined the effects of histamine H3 ligands on model animals of asthma and dementia. Using senescence accelerated mice, we evaluated their learning and memory ability by a shuttle box. Abnormally aged strain (P/8) mice were slow in acqusition of learning task, but the administration of H3 antagonist, thioperamide, facilitated the rate to the level of normal aged mice (R/1). A dementia mode mouse whose cholinergic system was destroyed by acopolamine showed an improvement in an elevated plus maze test by the administration of thioperamide. In various models of asthma, wa could not obtain clear results by H3 agonists such as (R)-alpha-methylhistamine and imitet. Probably a more suitable model of analysis is reguired for the evaluation of H3 agonists. A series of new H3 antagonists developed by Green Cross Co. were eraluated for their potency of inhibition of electric convulsion of mice : Among them AQ-145 was the most potent. Pharmacodynamic parameters of thioperamide and (R)-alpha-methylhistamine were measured in rats, showing that the penetration of these compounds into the brain is not good. During the course of these studies, it was found that H3 antagonists had anticonvulsive action in maximal electroshock model of mice. In summary, H3 antagonists may be a target for future development of antiepileptic and anti-dementia agents. However, to this purpose, it is necessary to carry out more basic studies.
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