Assessment of the enantiomeric purity of R- and S-N6-phenylisopropyladenosine (PIA): implications for adenosine receptor subclassification

Naunyn Schmiedebergs Arch Pharmacol. 1994 Jul;350(1):109-12. doi: 10.1007/BF00180020.

Abstract

A chiral column high-performance liquid chromatographic method was developed for the assessment of the enantiomeric purity of the stereoisomers of N6-phenylisopropyladenosine (PIA). The observed chiral purity of R-PIA was greater than 99.9%, whereas S-PIA was found to contain 4.4% of the R-enantiomer. In radioligand binding studies, the observed affinity of S-PIA for the adenosine A1 receptor (IC50 240 nM) could entirely be attributed to its content of R-PIA (IC50 7.8 nM). Calculation of a theoretical IC50 of pure S-PIA for the A2 receptor yielded a value of 6700 nM, which was 35-fold higher than for R-PIA (190 nM). Concludingly, the utilization of enantiomeric impure S-PIA in the definition of adenosine receptor subclasses is questionable.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Animals
  • Brain / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chromatography, High Pressure Liquid / methods*
  • Phenethylamines / metabolism
  • Phenylisopropyladenosine / chemistry
  • Phenylisopropyladenosine / isolation & purification*
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Receptors, Purinergic P1 / classification*
  • Receptors, Purinergic P1 / metabolism
  • Stereoisomerism
  • Xanthines / metabolism

Substances

  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Xanthines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Phenylisopropyladenosine
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Adenosine