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. 2009 Mar;5(1):63-73.
doi: 10.1007/s11302-008-9110-6. Epub 2008 Jun 21.

Selective P2X(7) receptor antagonists for chronic inflammation and pain

William A Carroll  1 , Diana Donnelly-Roberts, Michael F Jarvis
Affiliations

Selective P2X(7) receptor antagonists for chronic inflammation and pain

William A Carroll et al. Purinergic Signal. 2009 Mar.

Abstract

ATP, acting on P2X(7) receptors, stimulates changes in intracellular calcium concentrations, maturation, and release of interleukin-1beta (IL-1beta), and following prolonged agonist exposure, cell death. The functional effects of P2X(7) receptor activation facilitate several proinflammatory processes associated with arthritis. Within the nervous system, these proinflammatory processes may also contribute to the development and maintenance of chronic pain. Emerging data from genetic knockout studies have indicated specific roles for P2X(7) receptors in inflammatory and neuropathic pain states. The discovery of multiple distinct chemical series of potent and highly selective P2X(7) receptor antagonists have enhanced our understanding of P2X(7) receptor pharmacology and the diverse array of P2X(7) receptor signaling mechanisms. These antagonists have provided mechanistic insight into the role(s) P2X(7) receptors play under pathophysiological conditions. In this review, we integrate the recent discoveries of novel P2X(7) receptor-selective antagonists with a brief update on P2X(7) receptor pharmacology and its therapeutic potential.

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Figures

Fig. 1
Fig. 1
Historical P2X7 antagonists
Fig. 2
Fig. 2
Classes of small molecule P2X7 antagonist
Fig. 3
Fig. 3
Adamantane carboxamide P2X7 antagonists
Fig. 4
Fig. 4
Arylhydrazide P2X7 antagonists
Fig. 5
Fig. 5
Cyanoguanidine KATP opener 35 and P2X7 antagonist 36
Fig. 6
Fig. 6
Cyanoguanidine-piperazine P2X7 antagonists
Fig. 7
Fig. 7
Aryltetrazole and aryltriazole P2X7 antagonists
See this image and copyright information in PMC

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