The P2X(7) receptor is involved in several processes relevant to inflammation (cytokine release, NO generation, killing of intracellular pathogens, cytotoxicity), thus, it may be an appealing target for pharmacological intervention. The characterisation of native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective agonists and antagonists. BzATP is currently the most potent agonist known at the endogenous and recombinant P2X(7) receptor A tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. In this review article we have reported novel series of KN-62-related compounds of the general structure R(1)-Tyr(OR(2))-piperazinyl-R(3), in which three positions (R(1), R(2) and R(3)) were systematically varied. Two recent articles published by AstraZeneca have reported that novel series of cyclic imides and adamantane amides are potent P2X(7) receptor antagonists.