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A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity

Nature volume 268, pages 547–549 (1977)Cite this article

Abstract

METHIONINE and leucine enkephalin, the morphinomimetic pentapeptides from mammalian brain1–3 produce a weak and short-lived analgesia following intracerebroventricular (i.c.v) or intravenous (i.v.) administration to mice4 and rats5. β-endorphin6,7, 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. administration8–10, the pronounced effects of β-endorphin have led to the suggestion that it may be implicated in the aetiology of mental illness11–13. 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.

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Authors and Affiliations

  1. Biological and Medical Research Division, Sandoz Ltd, CH-4002, Basel, Switzerland

    DIETMAR ROEMER, HEINZ H. BUESCHER & RONALD C. HILL

  2. Chemical Research Pharmaceutical Division, Sandoz Ltd, CH-4002, Basel, Switzerland

    JANOS PLESS, WILFRIED BAUER, FRANCIS CARDINAUX, ANNEMARIE CLOSSE, DANIEL HAUSER & RENE HUGUENIN

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  1. DIETMAR ROEMER
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  2. HEINZ H. BUESCHER
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  3. RONALD C. HILL
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ROEMER, D., BUESCHER, H., HILL, R. et al. A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity. Nature 268, 547–549 (1977). https://doi.org/10.1038/268547a0

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