Stereoselectivity of NCS-382 binding to γ-hydroxybutyrate receptor in the rat brain
摘要：
γ-Hydroxybutyric acid (GHB), a naturally occurring metabolite of γ-aminobutyric acid (GABA), has been postulated to act both as a specific agonist of GHB receptors and as a weak GABA B receptor agonist. The racemic compound 6,7,8,9-tetrahydro-5-hydroxy-5 H -benzocyclohept-6-ylideneacetic acid ( RS -NCS-382), the only available antagonist of GHB receptors, has been resolved in two enantiomers, R - and S -; the potency of the latter to displace 4-hydroxy [2-3- 3 H] butyric acid ([ 3 H]GHB) and [ 3 H]NCS-382 from GHB receptors, on one hand, and [ 3 H]baclofen from GABA B receptors on the other was compared in rat brain homogenates. R -NCS-382 was found to be twice and 60 times more potent than the RS - and S -forms, respectively, in displacing [ 3 H]GHB and 2 and 14 times, respectively, in displacing [ 3 H]NCS-382 from GHB binding. Neither RS -NCS-382 nor its enantiomers inhibited [ 3 H]baclofen binding up to a concentration of 1 mM. Our results demonstrate that R -NCS-382 is the enantiomer of RS -NCS-382 with higher affinity for GHB receptors.
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关键词：
GHB (gamma-hydroxybutyrate) binding site RS-NCS-382 R-NCS-382 S-NCS-382 Baclofen GABA B receptor
DOI：
10.1016/S0014-2999(02)01713-2
被引量：
年份：
2002
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