Effect of (±)-methyl 3-ethyl-2,3,3a,4-tetrahydro-lH-indolo-[3,2,l-de][l,5]naphthyridine-6-carboxylate hydrochloride (OM-853), a new vincamine analogue, on the metabolism and function of cerebral serotonergic neurons
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- KODA Hirohumi
- Department of Pharmacology, Kyoto Prefectural University of 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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- KURIYAMA Kinya
- Department of Pharmacology, Kyoto Prefectural University of Medicine
書誌事項
- タイトル別名
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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 serotonergic neurons.
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説明
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 [14C]5-HT in striatal slices only at a high concentration (10-4 M). On the other hand, a low concentration of OM-853 (10-8-10-6 M) induced the increase of the spontaneous and high K+ (30 mM)-evoked releases of [14C]5-HT from striatal slices. OM-853 had more potent inhibitory effect on the binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-hydroxy DPAT) to 5-HT1A receptors and/or 5-HT autoreceptors than that of [3H]-ketanserin to 5-HT2 receptors. The stimulatory effect of OM-853 (10-7 M) on [14C]5-HT release was antagonized by 10-7 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.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 49 (3), 413-421, 1989
公益社団法人 日本薬理学会