| Co-Investigator(Kenkyū-buntansha) |
OHTSU Hiroshi Tohoku Univ.Pharmacology Assoc.Prof., 医学部, 助手 (60250742)
YANAI Kazuhiko Tohoku Univ.Pharmacology Assoc.Prof., 医学部, 講師 (50192787)
ONODERA Kinji Tohoku Univ.Pharmacology Assoc.Prof., 歯学部, 講師 (40133988)
MAEYAMA Kazutaka Ehime Univ.Pharmacology Prof., 医学部, 教授 (00157158)
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| Research Abstract |
Our major findings of the studies are as follows.
(1) When the histaminergic neuron system is activated pharmacologically, the duration periods of electroconvulsion are shortened. On the other hand, when the neuron is inactivated, the duration periods are prolonged. Thus, histamine is anticonvulsant.
(2) The threshold of electroconvulsion is lower in young mice (3 weeks) than in adult mice (>6 weeks), and the value is decreased further by an H1 antagonist, pyrilamine, but not by terfenadine, a non-sedative antihistaminic. These findings are consistnet with our clinical observation that the symptoms of some patients of epilepsy became worse when ketotifen was prescribed for allergic diseases, but they are well controlled when terfenadine was used.
(3) Thioperamide, an H3 antagonist, shoretend the latency in passive avoidance test of senescence accelerated mice. When the brain histamine level was decreased by treatment with an inhibitor of histidine decarboxylase, the death of neural cells
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in CA 2 region of the hippocampus of gerbils subjected to ischemia by a transient occlusion of the carotid arteries was promoted compared to control group. These findings suggest that the histaminergic system is involved in learning and memory processes.
(4) The double label autoradiography of a brain section was developed by taking advantage of the difference in the half-lives of 3H and 11C.The application of the method showed that H3 receptros are modulated by dopaminergic neurons through D1 receptors.
(5) The distribution of H1 receptors in the living human brain was mapped by PET with [11C] doxepin as a tracer. Its density decreased by aging in the ratio of 13 % per a decade. The density was higher in the foci of abnormal discharge of patients with complex partial seizure than in the opposite side, showing that the H1 receptors are up-regulated in the foci. The observation is in good agreement with the idea that brain histamine is anticonvulsant, which was obtained by pharmacological studies described above. The density was significantly lower in the cerebral cortices of patients of Alzheimer'disease or multiinfarct dementia than the age- and sex-matched normal controls. Less
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