Comparative study of analgesia induced by N VAL5- and Pro5-enkephalin analogs

We have compared the analgesic potency of N-Val5 analogs and Pro5 derivatives in order to identify the mechanism of the unusually strong antinociceptive activity induced by Pro5 enkephalin analogs. Whereas N-Val5 and Pro5 compounds are equiactive in in vitro assays, N-Val5 derivatives are considerably less active analgesics than Pro5 analogs. Since N-Val is the homolog of Pro with an opened pyrrolidine ring, these data show that the cyclic structure of Pro participates in the strong in vivo activity of Pro5 analogs without altering the binding to the opiate receptor.