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首页> 外文期刊>CNS drug reviews >A Review of Pharmacology of NCS-382, a Putative Antagonist of gamma-Hydroxybutyric Acid (GHB) Receptor.
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A Review of Pharmacology of NCS-382, a Putative Antagonist of gamma-Hydroxybutyric Acid (GHB) Receptor.

机译：NCS-382的药理学综述，它是γ-羟丁酸（GHB）受体的假定拮抗剂。

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gamma-Hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a semirigid compound structurally related to GHB, is the only compound reported to be an antagonist of the GHB receptor sites. In this article we review the in vivo and in vitro pharmacological properties of NCS-382 and its interaction with GHB and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a stereoselective ligand for GHB-binding sites, with both, the high and the low component of population, showing the same distribution of GHB receptors. Indeed, this compound did not display affinity for GABA(A), GABA(B), or any other known receptors, while conflicting data have been reported as to its selective antagonist action at GHB receptor. Only a few studies have shown that NCS-382 antagonizes GHB-induced effect, but a re-evaluation of all data reported in the literature suggests that the antagonistic effect of this compound could be due to an indirect action at GABA(B) receptors. As revealed by several behavioral studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced inhibition of locomotor activity and ataxia or suppression of operant responses. Moreover, it is capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive electrophysiological effects of endogenous and exogenous GHB observed in vivo have not been completely replicated in vitro. The only electrophysiological action of GHB antagonized in vitro by NCS-382 required a previous blockade of GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective antagonist for GHB receptor.
机译：γ-羟丁酸（GHB）是γ-氨基丁酸（GABA）的天然代谢产物，据推测可充当GHB受体的特异性激动剂和弱GABA（B）受体激动剂。迄今为止，在结构上与GHB相关的半刚性化合物6,7,8,9-四氢-5-羟基-5H-苯并环庚基-6-亚乙基乙酸（NCS-382）是唯一据报道可作为GHB拮抗剂的化合物。 GHB受体位点。在本文中，我们回顾了NCS-382的体内和体外药理特性及其与GHB和GABA（B）受体的相互作用。结合研究表明，NCS-382是GHB结合位点的立体选择性配体，具有高和低的总体含量，显示了GHB受体的相同分布。确实，该化合物对GABA（A），GABA（B）或任何其他已知受体均未表现出亲和力，尽管据报道其对GHB受体的选择性拮抗作用有矛盾的数据。只有少数研究表明NCS-382拮抗GHB诱导的作用，但是对文献中报道的所有数据的重新评估表明，该化合物的拮抗作用可能是由于对GABA（B）受体的间接作用。正如一些行为研究所揭示的那样，NCS-382不能拮抗GHB的歧视性刺激，GHB诱导的运动活动抑制和共济失调或抑制操作应答。而且，它能够在质量上引起与GHB相似的作用，或增强GHB的某些作用。此外，体内观察到的内源性和外源性GHB的NCS-382敏感性电生理效应尚未在体外完全复制。 NCS-382在体外拮抗的GHB的唯一电生理作用需要事先阻断GABA（B）受体。我们得出的结论是，NCS-382是一种良好的配体，但不是GHB受体的选择性拮抗剂。

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