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Ups J Med Sci. 2000;105(1):1-15.

From opiate pharmacology to opioid peptide physiology.

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Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.


This is a personal account of how studies of the pharmacology of opiates led to the discovery of a family of endogenous opioid peptides, also called endorphins. The unique pharmacological activity profile of opiates has an endogenous counterpart in the enkephalins and beta-endorphin, peptides which also are powerful analgesics and euphorigenic agents. The enkephalins not only act on the classic morphine (mu-) receptor but also on the delta-receptor, which often co-exists with mu-receptors and mediates pain relief. Other members of the opioid peptide family are the dynorphins, acting on the kappa-receptor earlier defined as precipitating unpleasant central nervous system (CNS) side effects in screening for opiate activity, A related peptide, nociceptin is not an opioid and acts on the separate NOR-receptor. Both dynorphins and nociceptin have modulatory effects on several CNS functions, including memory acquisition, stress and movement. In conclusion, a natural product, morphine and a large number of synthetic organic molecules, useful as drugs, have been found to probe a previously unknown physiologic system. This is a unique development not only in the neuropeptide field, but in physiology in general.

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