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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Endomorphin analogs.

Opiate alkaloids, such as morphine, are powerful analgesic agents that are the drugs of choice for the treatment of severe pain. The pharmacological effects of opiates are mediated through the binding and activation of membrane-bound opioid receptors that are found in the central and peripheral nervous systems. Opioid receptors have been classified into three different types, mu, delta and kappa, and are activated by the specific ligands. It has been demonstrated that the most potent antinociceptive effects are mediated by the mu-receptor. However, until 1997 no endogenous ligand for this receptor was known. The identification of endomorphins opened a new era in the research of the mu-opioid system. They are the first reported brain peptides that label mu-receptor with high affinity and selectivity and therefore are proposed as the endogenous mu-opioid receptor ligands. Morphine and endomorphins act as agonists at the same mu-opioid receptor, but the latter are thought to inhibit pain without some of the undesired side-effects of plant opiates. This observation encouraged extensive studies on the possible use of endomorphin analogs as analgesics instead of morphine. This review summarizes a decade of research on structure-activity relationship studies of endomorphin analogs, aimed at obtaining compounds with increased bioavailability, in particular with better barrier penetration and resistance against enzymatic degradation. Chemical modifications that led to obtaining potent and selective agonists and antagonists based on the structure of endomorphins are discussed.[1]


  1. Endomorphin analogs. Janecka, A., Staniszewska, R., Fichna, J. Curr. Med. Chem. (2007) [Pubmed]
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