(3-Aminocyclopentyl)methylphosphinic acids: novel GABA(C) receptor antagonists

Neuropharmacology. 2007 Mar;52(3):779-87. doi: 10.1016/j.neuropharm.2006.09.014. Epub 2006 Nov 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • GABA Agonists / pharmacology
  • GABA Antagonists / chemistry*
  • GABA Antagonists / pharmacology*
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Potentials / radiation effects
  • Oocytes
  • Organophosphorus Compounds / chemistry*
  • Organophosphorus Compounds / pharmacology*
  • Patch-Clamp Techniques / methods
  • Receptors, GABA / physiology
  • Xenopus laevis
  • gamma-Aminobutyric Acid / pharmacology


  • GABA Agonists
  • GABA Antagonists
  • GABA-C receptor
  • Organophosphorus Compounds
  • Receptors, GABA
  • 3-aminopropyl(methyl)phosphinic acid
  • gamma-Aminobutyric Acid