Assessment of the enantiomeric purity of R- and S-N6-phenylisopropyladenosine (PIA): implications for adenosine receptor subclassification.
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.
Mathôt
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RA
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Van den Aarsen
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BC
von Frijtag Drabble Künzel
J K
JK
Danhof
M
M
Ijzerman
A P
AP
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010627:Phenethylamines / Q000378:metabolism; D010660:Phenylisopropyladenosine / Q000737:chemistry / Q000302:isolation & purification*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000145:classification* / Q000378:metabolism; D013237:Stereoisomerism; D014970:Xanthines / Q000378:metabolism
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010660:Phenylisopropyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine