Selective P2X7 receptor antagonists for chronic inflammation and pain

被引：92

作者：

Carroll, William A. ^{[1
]}

Donnelly-Roberts, Diana ^{[1
]}

Jarvis, Michael F. ^{[1
]}

机构：

[1] Abbott Labs, Neurosci Res, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA

来源：

PURINERGIC SIGNALLING | 2009年 / 5卷 / 01期

关键词：

Calcium flux; Pore formation; Pain; Inflammation; Interleukin-1; Nerve injury; Microglia; Hyperalgesia; Neural-glial interactions; ACTIVATED PROTEIN-KINASE; POTASSIUM CHANNEL OPENERS; IN-VITRO ACTIVITY; NEUROPATHIC PAIN; NUCLEOTIDE RECEPTOR; OVERACTIVE BLADDER; DEFICIENT MICE; PORE FORMATION; P2; RECEPTORS; ATP;

D O I：

10.1007/s11302-008-9110-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

ATP, acting on P2X(7) receptors, stimulates changes in intracellular calcium concentrations, maturation, and release of interleukin-1 beta (IL-1 beta), 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.

引用

页码：63 / 73

页数：11

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