ADENOSINE RECEPTOR ANTAGONISTS

ADENOSINE RECEPTOR ANTAGONISTS block adenosine receptors, activation of which has a wide range of mainly inhibitory actions in the body (see ADENOSINE RECEPTOR AGONISTS). Subtypes of adenosine receptors include A1, A2A, A2B and A3. Most selective antagonists used experimentally are xanthine analogues: these include 8-SPT (8-sulphophenyItheophylline), DPCPX (8-cyclopentyl-1,3-dipropylxanthine) and CSC (8-chlorostyrylcaffeine). At A1 receptors, DPCPX is a relatively selective antagonist. At A2a receptors, ZM 241385, SCH 58261 and CSC are relatively selective antagonists. At A2B receptors there are no established antagonists. There is some evidence suggesting these receptors as possible therapeutic targets for antagonists in treating asthma and allergic lung disease. At A3 receptors relatively selective antagonists include: L 268605, MRS 1191 and BWA1433.

Although not selective or potent, some of the wide-ranging pharmacological actions of a number of naturally occurring methylxanthine drugs and their derivatives (e.g. aminophylline. caffeine, theobromine, theophylline) are thought to result from their adenosine receptor antagonist properties (however, they also act as PHOSPHODIESTERASE INHIBITORS). Though they are rather inactive as adenosine antagonists, flavinoids (e.g. galangin) are consumed in dietary quantities sufficient to have relevant pharmacological actions. Also, though much less active than as calcium-channel blockers, agents such as nitrendipine, nicardipine and nifedipine have a low affinity at A3 receptors.