Our understanding of the role GABA(C) receptors play in the central nervous system is limited due to a lack of specific ligands. Here we describe the pharmacological effects of (+/-)-cis-3- and (+/-)-trans-3-(aminocyclopentyl)methylphosphinic acids ((+/-)-cis- and (+/-)-trans-3-ACPMPA) as novel ligands for the GABA(C) receptor showing little activity at GABA(A) or GABA(B) receptors. (+/-)-cis-3-ACPMPA has similar potency to (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at human recombinant rho1 (K(B)=1.0+/-0.2microM) and rat rho3 (K(B)=5.4+/-0.8microM) but is 15 times more potent than TPMPA on human recombinant rho2 (K(B)=1.0+/-0.3microM) GABA(C) receptors expressed in Xenopus oocytes. (+/-)-cis- and (+/-)-trans-3-ACPMPA are novel lead compounds for developing into more potent and selective GABA(C) receptor antagonists with increased lipophilicity for in vivo studies.

中文翻译：

---

（3-氨基环戊基）甲基次膦酸：新型GABA（C）受体拮抗剂。

由于缺乏特定的配体，我们对GABA（C）受体在中枢神经系统中的作用的理解受到限制。在这里我们描述（+/-）-顺3和（+/-）-反3-（氨基环戊基）甲基次膦酸（（+/-）-顺3和（+/-）-反-3-ACPMPA）作为GABA（C）受体的新型配体，对GABA（A）或GABA（B）受体几乎没有活性。（+/-）-cis-3-ACPMPA在人重组rho1上具有与（1,2,5,6-四氢吡啶-4-基）甲基次膦酸（TPMPA）相似的效价（K（B）= 1.0 +/- 0.2 microM）和大鼠rho3（K（B）= 5.4 +/- 0.8microM），但对人重组rho2（K（B）= 1.0 +/- 0.3microM）GABA（C）受体的效力比TPMPA强15倍爪蟾卵母细胞。