The P2X7 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 P2X7 receptor continues to be hindered by the lack of specific and subtypeselective agonists and antagonists. BzATP is currently the most potent agonist known at the endogenous and recombinant P2X7 receptor A tyrosine derivative named KN-62 exhibits selective P2X7 receptor-blocking properties. In this review article we have reported novel series of KN-62-related compounds of the general structure R1-Tyr(OR2)-piperazinyl-R3, in which three positions (R1, R2 and R3) were systematically varied. Two recent articles published by AstraZeneca have reported that novel series of cyclic imides and adamantane amides are potent P2X7 receptor antagonists.