Analgesic properties of chimeric peptide based on morphiceptin and PFRTic-amide

摘要

A chimeric opioid peptide (MCRT, YPFPFRTic-NH 2) was here designed and synthesized. This peptide was based on morphiceptin (YPFP-NH 2) and a neuropeptide FF (NPFF) derivative (PFRTic-NH 2) sharing one proline. This peptide is intended to produce potent analgesia. MCRT was found to induce analgesic activity in a dose- and time-dependent manner, as indicated by a tail flick latency test in mice to which it had been intracerebroventricularly administered (5-60min, 0.025-2.5nmol/kg (0.5-50pmol per mouse), ED 50=1.49nmol/kg). At 2.5nmol/kg, MCRT showed significantly higher levels of analgesic activity than morphiceptin or PFR(Tic)amide at 2500nmol/kg. Naltrindole and cyprodime were found to partially but significantly inhibit this analgesic activity, but naloxone blocked it completely. The kappa opioid receptor antagonist nor-BNI was found to slightly inhibit MCRT and morphiceptin. Pre-injection of BIBP3226 and co-administration of NPFF and MCRT showed that NPFF receptors were involved in the analgesia of MCRT. BIBP3226 was found to weaken the analgesic effects of MCRT, but BIBP3226 could not block the analgesic effects of PFR(Tic)amide. Overall, MCRT was found to have stronger analgesic activity than morphiceptin or PFR(Tic)amide when interacting with mixed μ/δ opioid receptor interactions. MCRT also showed partial interaction with NPFF receptors.