From Opiate Pharmacology to Opioid Peptide Physiology

Abstract

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 β-endorphin, peptides which also are powerful analgesics and euphorigenic agents. The enkephalins not only act on the classic morphine (μ-) receptor but also on the δ-receptor, which often co-exists with μ-receptors and mediates pain relief. Other members of the opioid peptide family are the dynorphins, acting on the κ-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.