Phosphinic, phosphonic and seleninic acid bioisosteres of isonipecotic acid as novel and selective GABA(C) receptor antagonists

Neurochem Int. 2003 Jun;42(7):561-5. doi: 10.1016/s0197-0186(02)00162-6.


A number of amino acids bioisosterically derived from the specific GABA(A) agonist, isonipecotic acid, were electrophysiologically characterized as antagonists at GABA(C) rho(1) receptors expressed in Xenopus oocytes. The phosphinic acid analogue of isonipecotic acid, piperidin-4-ylphosphinic acid (2), was comparable with the standard GABA(C) antagonist, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), in terms of potency and GABA(C) versus GABA(A) receptor selectivity. Whereas the phosphonic acid analogue, piperidin-4-ylphosphonic acid (4), was at least an order of magnitude weaker than piperidin-4-ylphosphinic acid as a GABA(C) antagonist, the seleninic acid analogue, piperidin-4-ylseleninic acid (SEPI, 6), was the most potent and selective GABA(C) antagonist within the group of isonipecotic acid derived amino acids studied.

MeSH terms

  • Animals
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Female
  • GABA Antagonists / pharmacology*
  • Humans
  • Isonipecotic Acids / chemistry*
  • Oocytes
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Phosphinic Acids / chemistry
  • Phosphinic Acids / pharmacology*
  • Protein Isoforms / drug effects
  • Receptors, GABA / drug effects*
  • Xenopus laevis


  • Carboxylic Acids
  • GABA Antagonists
  • GABA-C receptor
  • Isonipecotic Acids
  • Organophosphonates
  • Organoselenium Compounds
  • Phosphinic Acids
  • Protein Isoforms
  • Receptors, GABA
  • seleninic acid