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The synthesis and preliminary pharmacological in vitro of seventeen pentapeptide analogs of the opioid peptide dermorphin are reported. Substitution at residue Tyr5 and/or modification of C-terminal are generally well tolerated.

Characterisation and pharmacological data of twelve synthetic tetrapeptide analogs of dermorphin (opioid heptapeptide) are reported. An N-terminal tetrapeptide free acid or ester is less potent that the corresponding amide. Whereas substitution of Gly4 by another aminoacid residue is well tolerated, substitution of D-Ala2 by D- or L-alpha-aminoxypropionic acid causes a complete loss of activity. Finally, guanidination of the tetrapeptides results in an increase of peripheral and central opioid activity.

The synthesis and pharmacological activity of Leu-enkephalins carrying a free or substituted carboxymethyl group at glycine-2-nitrogen are described.

Preliminary pharmacological data and the characterization of sixteen synthetic tetrapeptide-amide analogs of dermorphin (opioid heptapeptide) are reported. N,N-dialkylamides displayed reduced or no activity; on the contrary, derivatization of H-Tyr-D-Ala-Phe-Gly-OH C-terminus by suitable amide moieties (1-adamantanamine, 1-adamantane-methylamino, or D-alpha-methylbenzylamine) produced potent analogues with peripheral and central opioid activities comparable to, or higher than those of dermorphins.

The preliminary pharmacological activity pattern in guinea pig ileum and mouse vas deferens bioassays of five dermorphin related tetrapeptides is reported. The biological activities of the compounds under examination appear to be correlated in a statistically significant way to the lipophilic character of the C-terminal substituents.

We describe the synthesis and preliminary in vitro and in vivo pharmacological tests of six [beta-Ala4]tetrapeptides analogs of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. The modification obtained by substituting beta-Ala4 for Gly4 provided further analogues with significant opioid activity.

The preliminary pharmacological data on synthetic peptides related to dermorphin (opiate-heptapeptide) are reported. The tetrapeptide, corresponding to the N-terminal sequence of dermorphin is a minimum requirement for significant opiate-activity in vitro.

By employing the mouse tail-flick assay the analgesic activity of selected dermorphin tetrapeptides was assessed. The remarkable differences in potency exhibited by peptides after i.c.v. (500-1000 times higher than morphine) and s.c. (nearly comparable to morphine) administration are probably due to peptidase degradation.

We describe the synthesis and preliminary in vitro and in vivo pharmacological tests of five endothiotetrapeptide analogues of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser.-NH2. The modification obtained by substituting Phet for Phe3 or Glyt for Gly4 provided further analogues with significant opioid activity.