Аннотация
A variety of alkylxanthines has been comparatively examined as antagonists
of A1 adenosine receptors in rat fat cells, rat and bovine cerebral
cortex and of A2 adenosine receptors in human platelets. With few
exceptions all xanthine derivatives with 7-position substituents
such as diprophylline, proxyfylline, pentoxifylline and etofylline
were less potent antagonists than xanthine itself which had Ki-values
of 170 mumol/l (A1) and 93 mumol/l (A2). Theophylline, caffeine and
3-isobutyl-1-methylxanthine were more potent than xanthine but nearly
equipotent antagonists at both receptor subtypes. 8-Phenyl substituents
considerably increased the antagonist potency at A1 and A2 receptors.
1,3-Diethyl-8-phenylxanthine was the most potent A2 antagonist (Ki
0.2 mumol/l) in human platelets. At A1 receptors 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
(PACPX) was the most potent antagonist in all three tissues with
Ki-values from 0.3 to 8.6 nmol/l. Several 8-phenylxanthine derivatives
were remarkably selective antagonists at A1 receptors. 8-Phenyltheophylline
was approximately 700 times more potent as antagonist at A1 receptors
(bovine brain) than at A2 receptors (human platelets), and PACPX
was even 1,600 times more potent as A1 adenosine receptor antagonist.
These compounds offer a possibility for a subtype-selective blockade
of adenosine receptors.
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