PACPX--a substituted xanthine--antagonizes both the A1 and A2 subclasses of the P1-purinoceptor: antagonism of the A2 subclass is competitive but antagonism of the A1 subclass is not.

1,3-Dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) was examined for its ability to antagonize adenosine acting on the A1 and A2 subclasses of the P1-purinoceptor. A1-purinoceptors were studied in the isolated, driven left atria of the guinea-pig, and A2-purinoceptors in the isolated, carbachol-contracted taenia coli of the guinea-pig. PACPX antagonized the actions of adenosine in both types of preparation and was a more potent antagonist than 8-phenyltheophylline. The antagonism at the A2-purinoceptor was competitive with a pA2 of 5.95. The antagonism at the A1-purinoceptor was not competitive, although antagonism at the A1-purinoceptor was greater than that at the A2-purinoceptor, based on a comparison of pD2 values. The manner of antagonism of PACPX on the A1-purinoceptors of the heart was different from that found for the A1-receptors in bovine brain, implying that there is a fundamental difference between these central and peripheral A1 subclasses of P1-purinoceptor.