3-Chloro,4-methoxyfendiline is a potent GABA_B receptor potentiator in rat neocortical slices

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• 作者：Ong ; Jennifer ; Parker ; David A.S. ; Marino ; Victor ; Kerr ; David I.B. ; Puspawati ; Ni Made ; Prager ; Rolf H.
• 关键词：Neocortex ; Baclofen ; 3-Chloro ; 4-methoxyfendiline ; Pre- and postsynaptic GABA_B receptor ; (Rat)
• 刊名：European Journal of Pharmacology
• 出版年：2005
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：January 10, 2005
• 卷：507
• 期：1-3
• 页码：35-42
• 文件大小：217 K

摘要

Using grease-gap recording from rat neocortical slices, the GABA_B receptor agonist baclofen elicited reversible and concentration-dependent hyperpolarizing responses (EC₅₀=18±2.3 μM). The hyperpolarizations were antagonised by the GABA_B receptor antagonist Sch 50911 [(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid). (+)-N-1-(3-chloro-4-methoxyphenyl)ethyl-3,3-diphenylpropylamine (3-chloro,4-methoxyfendiline; 3-Cl,4-MeO-fendiline) reversibly potentiated baclofen-induced hyperpolarizing responses, which were reduced by Sch 50911, producing leftward shifts of the baclofen concentration–response curves, with a marked increase in the maximal hyperpolarization (EC₅₀=2±0.5 μM). In slices preincubated with either [³H]GABA or [³H]glutamic acid, 3-Cl,4-MeO-fendiline (1 μM) potentiated the inhibitory effect of baclofen (2 μM) on the electrically evoked release of [³H]GABA and had a similar effect on the release of [³H]glutamic acid at a concentration of 0.5 μM, without affecting the basal release. These effects were blocked by Sch 50911 (10 μM). Our findings suggest that 3-Cl,4-MeO-fendiline is a potent potentiator of pre- and postsynaptic GABA_B receptor-mediated functions.