Effects of JL 3, a putative antidepressant, on rat noradrenergic and serotonergic systems

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• 作者：Lié ; geois ; Jean-Franç ; ois ; Seutin ; Vincent ; Scuvé ; e-Moreau ; Jacqueline ; et. al.
• 关键词：Electrophysiology ; Antidepressant ; 5-HT_1A receptor ; α ; ₂-Adrenoceptor ; Tyramine ; Norepinephrine transporter ; Pyridobenzoazepine
• 刊名：European Journal of Pharmacology
• 出版年：1999
• 出版时间：December 15, 1999
• 年：1999
• 卷：386
• 期：2-3
• 页码：211-216
• 全文大小：264 K

文摘

Using in vitro electrophysiological procedures, we confirm the inhibitory effect of 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine (JL 3), on dorsal raphe serotonergic (IC₅₀=14 μM) and noradrenergic neurons (IC₅₀=4.5 μM). The effect on dorsal raphe neurons was reduced by N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide (WAY-100635), suggesting the importance of 5-HT_1A receptor stimulation. Yohimbine, and ritanserin, to a lesser extent, blocked the inhibitory effect of JL 3 on locus coeruleus neurons indicating that α₂-adrenoceptors and 5-HT_2A receptors may be implicated in the effects. Because of its negligible α₂-adrenoceptor affinity, the effect of JL 3 on locus coeruleus neurons, would have to be indirect. JL 3 may interfere with the norepinephrine transporter site (IC₅₀=0.34 μM). JL 3 tended to reinforce the hypertensive effect of norepinephrine, while it strongly inhibited the hypertensive effect of tyramine, further indicating an interaction at the norepinephrine transporter site level.