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In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.
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