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The general pharmacological actions of N-acetoacetyl-3-hydroxytyrosine (L-DOPA acetoacetate) were investigated and compared with those of L-3, 4-dihydroxypenylalanine (L-DOPA). The following results were obtained. 1) L-DOPA acetoacetate and L-DOPA suppressed slightly the spontaneous motor activity in mice. 2) L-DOPA acetoacetate and L-DOPA showed no effect on the sleeping time induced by hexobarbital and on maximal electroshock-, pentetrazol- and strychnine-convulsions in mice, but maximal electroshock convulsion was inhibited by the combined administration of L-DOPA and a monoamine oxidase inhibitor, pargyline. 3) L-DOPA acetoacetate and L-DOPA suppressed the squirming induced by acetic acid in mice. 4) L-DOPA acetoacetate did not have a hypothermic action in mice although L-DOPA did slightly. 5) In anaesthetized rats, L-DOPA acetoacetate and L-DOPA produced a slight temporary rise in the blood pressure and potentiated the pressor actions of norepinephrine and tyramine. The tyramine-induced tachyphylaxis and the abolishment of the response of tyramine induced with reserpine pretreatment were restored by both compounds. 6) On the isolated smooth muscle preparations such as guinea-pig vas deferens, intestine, aorta, rabbit aorta and rat uterus, the contractions induced by several agonists were almost unaffected by L-DOPA acetoacetate and L-DOPA. On guinea-pig vas deferens, aorta and rabbit aorta preparations, however, the tyramine-induced tachyphylaxis and the abolishment of the response of tyramine induced with reserpine pretreatment were restored by both compounds. These restorations were not observed by the treatment of a peripheral DOPA decarboxylase inhibitor, Ro4-4602. These actions were also found on guinea-pig atria preparations. Furthermore, on rat uterus preparations, both compounds increased the spontaneous motility. 7) On the gastrointestinal propulsion in mice and on the isolated skeletal muscle preparations in frog, L-DOPA acetoacetate and L-DOPA showed no effect. From the results mentioned above, it could be assumed that L-DOPA acetoacetate possessed only peripheral without central action though L-DOPA possessed both of central and peripheral actions, and that the activities would be due to their metabolites.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 23 (9), 2075-2086, 1975
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204174088576
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- NII論文ID
- 110003622156
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- PubMed
- 1182915
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可