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[摘要]：After the rise and fall of cyclooxygenase-2 (COX-2)-selective inhibitors as safe replacements for nonsteroidal antiinflammatory drugs (NSAIDs), particularly for the treatment of chronic painful conditions in the elderly, there is still a great need for safer drugs that can alleviate both inflammation and pain. Des-arginine metabolites of bradykinin-related peptides are involved in the propagation and maintenance of inflammation and pain via activation of bradykinin B(1) receptors, the bradykinin receptor subtype that is hardly detectable in healthy tissues but induced during inflammation. Due to the really inducible nature of the receptor at peripheral sites, orally acting B(1) receptor antagonists hold the promise of being a safe substitute for NSAIDs, especially for chronic treatment. In addition, nonclinical research suggests the potential utility of central nervous system-penetrating B(1) receptor antagonists in a broader range of chronic pain states, including neuropathic pain, and involving a central sensitization process. However, exploitation of the therapeutic utility has been hindered by the extreme difficulties related to optimization for an inducible peptide-receptor with species-specific differences in physiology and pharmacology. The scientific literature implicating therapeutic utility for B, receptor antagonists and the ongoing efforts for exploiting this target are reviewed in this article. |
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