The treatment of the neurogenic component of inflammatory diseases and neuropathic pain remains an unresolved issue in pharmacotherapy. A novel endogenous antiinflammatory/analgesic mechanism mediated by somatostatin released from capsaicin-sensitive sensory nerve terminals has been identified and reported by our research group. These findings raised the possibility of targeting somatostatin receptors to decrease inflammation and nociception. Native somatostatin cannot be used in clinical practice due to its short plasma half-life and broad range of actions, but stable and selective synthetic analogues might open new perspectives for drug development. A cyclic heptapeptide analogue, TT-232, showing the greatest affinity for the somatostatin sst4 receptor subtype was synthesized at the Peptide Chemistry Research Group of the Hungarian Academy of Sciences and proved to have no endocrine activity. On the other hand, it exerted significant inhibitory effects in several acute and chronic inflammatory and nociceptive animal models, including chronic arthritis, mono- and polyneuropathy conditions. TT-232 is therefore considered a promising lead molecule for the development of a completely new type of antiinflammatory/analgesic agents.
ASJC Scopus subject areas
- Pharmacology (medical)