Effect of (.+-.)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo-(3,2,1-de)(1,5) naphthyridine-6-carboxylate hydrochloride (OM-853), a new vincamine analogue, on the metabolism and function of cerebral serotonergic neurons.
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概要
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Effect of (±)-methyl 3-ethyl-2, 3, 3a, 4-tetrahydro-1H-indolo[3, 2, 1-de] [1, 5] naphthyridine-6-carboxylate hydrochloride (OM-853), a new vincamine analogue, on the metabolism and function of cerebral 5-hydroxytryptamine (5-HT) neurons was investigated using male Wistar rats. The single administration of OM-853 (200 mg/kg, p.o.) induced the facilitation of metabolic turnover of 5-HT in various brain areas except the cerebral cortex, pons-medulla and cerebellum. In vitro addition of OM-853 inhibited the uptake of [<SUP>14</SUP>C]5-HT in striatal slices only at a high concentration (10<SUP>-4</SUP> M). On the other hand, a low concentration of OM-853 (10<SUP>-8</SUP>-10<SUP>-6</SUP> M) induced the increase of the spontaneous and high K<SUP>+</SUP> (30 mM)-evoked releases of [<SUP>14</SUP>C]5-HT from striatal slices. OM-853 had more potent inhibitory effect on the binding of [<SUP>3</SUP>H]8-hydroxy-2-(di-n-propylamino)tetralin (8-hydroxy DPAT) to 5-HT<SUB>1A</SUB> receptors and/or 5-HT autoreceptors than that of [<SUP>3</SUP>H]-ketanserin to 5-HT<SUB>2</SUB> receptors. The stimulatory effect of OM-853 (10<SUP>-7</SUP> M) on [<SUP>14</SUP>C]5-HT release was antagonized by 10<SUP>-7</SUP> M 8-hydroxy DPAT, which is known to act at presynaptic 5-HT autoreceptors as an agonist. These results suggest that OM-853 may induce facilitation of 5-HT turnover by enhancing 5-HT release, probably via the inhibition of presynaptic 5-HT autoreceptor.
- 公益社団法人 日本薬理学会の論文
著者
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Katsura Masashi
Department Of Mathematics Faculty Of Science Kyoto Sangyo University
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Kuriyama Kinya
Department Of Health Promoting Acupuncture And Moxibution Meiji University Of Oriental Medicine
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Hashimoto Tsuneichi
Department Of Pharmacology Kyoto Prefectural University Of Medicine
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KATSURA Masashi
Department of Pharmacology, Kyoto Prefectural University of Medicine
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KODA Hirohumi
Department of Pharmacology, Kyoto Prefectural University of Medicine
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