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• W1598385871 abstract "The bradykinin B2 receptor is a mature G-protein coupled receptor target that has long offered the prospect of therapeutic intervention in pain and inflammation, but this has been notoriously difficult to achieve. This chapter discusses the kinin B2 receptor as a therapeutic target, peptide bradykinin B2 receptor antagonists, and non-peptide bradykinin B2 receptor antagonists. The cloned human B2 receptor is composed of 364 amino acids and is phylogenetically only 36% identical to the human B1 receptor. In contrast to the B1 subtype, B2 receptors are expressed constitutively in most cell and tissue types and mediate most of the known effects of BK and KD when these are produced in plasma and tissues, respectively. There is evidence that activation of B2 receptors engages multiple signal transduction pathways, leading to production of pro-inflammatory cytokines, such as interleukin-1β, and induction of the transcriptional nuclear factor-κB. These entities are subsequently capable of inducing the upregulation and expression of B1 receptors, potentiating the inflammatory response further. Potent, selective and orally active non-peptide B2 receptor antagonists have emerged as potential therapeutic agents and have demonstrated efficacy in various animal models of inflammatory pain. However, although most patent applications cite pain as a major indication, no B2 antagonist has been successfully shepherded through clinical trials to registration, despite a substantial industry-wide preclinical effort." @default.
• W1598385871 created "2016-06-24" @default.
• W1598385871 creator A5072773759 @default.
• W1598385871 date "2004-01-01" @default.
• W1598385871 modified "2023-10-16" @default.
• W1598385871 title "Bradykinin B2 Receptor Antagonists for the Treatment of Pain" @default.
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• W1598385871 doi "https://doi.org/10.1016/s0065-7743(04)39009-3" @default.
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