Structure-activity Study of Endomorphins Analogs with Cterminal Substitution

摘要

Aims: To further wonder the influence of C-terminal residues on the pharmacological activities. Methods: The in vitro and in vivo opioid activities of C-terminal substitution analogs [L-Tic~4] EM1 and [L-Tic~4] EM2 were investigated using radioligand binding assay, guinea pig ileum (GPI) assay, mouse vas deferens (MVD) assay, systemic arterial pressure (SAP) assay and tail-flick test. Results: Our data showed that the analogs produced a higher δ-opioid affinity but low μ-opioid affinity, dose-dependent but reduced analgesic activities and cardiovascular effect comparing with those of EMs. Moreover, these effects induced by the analogs can be inhibited by naloxone, indicating an opioid mechanism. Conclusion: These results provided suggestive evidences that the substitution of C-terminal residue may play an important role in the regulation of opioid affinities and pharmacological activities.