Discovery of Stable Non-opioid Dynorphin A Analogues Interacting at the Bradykinin Receptors for the Treatment of Neuropathic Pain.

ABSTRACT: Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg⁷]-Dyn A-(4-11), which shows good binding affinity (IC₅₀ = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals. However, 1 has a serious drawback as a potential drug candidate for the treatment of neuropathic pain because of its susceptibility to enzymatic

SUBMITTER: Hall SM 

PROVIDER: S-EPMC5689068 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature