A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity

METHIONINE and leucine enkephalin, the morphinomimetic pentapeptides from mammalian brain 1–3 produce a weak and short-lived analgesia following intracerebroventricular (i.c.v) or intravenous (i.v.) administration to mice 4 and rats 5 . β-endorphin 6,7 , another morphinomimetic fragment of β-lipotropin but with 31 amino acid residues, shares its amino-terminal sequence with met-enkephalin. In addition to showing marked and long-lived analgesic activity following i.c.v. and i.v. administration 8–10 , the pronounced effects of β-endorphin have led to the suggestion that it may be implicated in the aetiology of mental illness 11–13 . We report here a number of the pharmacological properties of five synthetic pentapeptides structurally related to met-enkephalin, two of which exhibit significant analgesic activity after oral administration and which are more potent analgesics administered parenterally than β-endorphin.