Abstract

TRPV1 is a ligand-gated non-selective cation channel that is considered to be an important pain integrator. Capsaicin, the prototypical TRPV1 agonist, has a clear therapeutic potential. In this letter, for lowering its pungency, a series of nitric oxide-releasing derivatives of capsaicin were designed and synthesized, including 10 compounds which were the direct combination of capsaicin and dihydro capsaicin with various nitric oxide donors. Preliminary biological tests suggested the compounds had both TRPV1 agonist activity and nitric oxide release activity. Compound B2, B5, B8 had better analgesic activity than capsaicin. Based on these results, Compound B2, B5, B8 can be considered as lead candidates for the further development of analgesic drugs.

Keywords: Analgesia Drugs, Nitric Oxide-Releasing, Capsaicin Derivatives, TRPV1 Agonist, channel, Pain, vanilloid receptor, desensitization, Nitric oxide, NO synthase, HEK, glutamine, KRH, KRH buffer, Ca2, dihydro capsaicin, spectrometer, Na2SO4, TLC, filtrate, furazan ring