Comparison of the analgesic properties of lipotropin C-fragment and stabilized enkephalins in the rat

The C-Fragment of lipotropin (LPH 61–91) was shown to produce strong and long-lasting analgesia on intraventricular infusion in the rat. Its analgesic properties were compared with those of three synthetic derivatives of methionine enkephalin (LPH 61–65) which had been stabilized against enzymic degradation by blocking one or both termini with N-methyl and C-amide groups. C-Fragment was approximately 50 times more potent on a molar basis than N-methyl methionine enkephalin amide. The singly blocked pentapeptides, like methionine enkephalin, produced little more than transient analgesia. It was concluded that the analgesic properties of C-Fragment depend on the length and nature of the peptide chain rather than on the resistance of its N-terminal pentapeptide to degradation.