Effects And Mechanisms Within Endomorphin-1 Analogues On Human Sperm Motility

To search novel endomorphin-1 analogues exhibit good analgesic effects with minimal implications for human sperm motility.Methods: A new class of endomorphin-1(EM-1)analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification,Phe4 was chlorinated,D-Ala-Gly Substituted L-Pro2.Their bioactivities were measured by radioligand binding assay,metabolic stability,antinociception activity and sperm motility effects.Results: In radioligand binding assays,analogue GAGPC(Nα-Amidino-Tyr-D-Ala-Gly-Trp-p-Cl-Phe-NH2),shown a μ-opioid receptor affinity about 1.42-fold higher and a 2.40-fold higher δ-opioid receptor affinity than EM-1.In the metabolic stability assays,GAGPC had the longest half-lives which was 279.7 min(57-fold higher than that of EM-1).In the tail-flick test in mice,GAGPC showed best analgesia in these analogues.In sperm motility assays,GAGPC(10-7M,10-6M)decreased the percentage of a+b% grade,but when the concentration incresed to(10-5M),it is not significantly compared with initial value.At the same concentration,morphine caused significant reduction after 60 minutes.Conclusion: we found that analogues GAGPC,activating μ-opioid receptor and partial δ-opioid receptor,exhibit good analgesic effects with minimal implications for human sperm motility.It might be of importance in potential application as drug candidates as analgesic without implications for human sperm motility.