Endogenous Opioid Peptides

A seminal discovery during the 1960s and 1970s was the presence of endogenous substances in mammalian brain that appeared to possess the pharmacological qualities of morphine and other opioid analgesics. It had been known for quite awhile that most "drug receptors" were in fact receptors for endogenous transmitters. It was surprising, therefore, when tissue from mouse brain was shown to avidly bind opioids, such as morphine and heroin, in a stereoselective manner. As Avram Goldstein, one of the pharmacologists involved in discovering the endogenous opioids, noted, "It seemed unlikely, a priori, that such highly stereo-specific receptors should have been developed by nature to interact with alkaloids from the opium poppy."1

A series of peptides, occurring naturally in brain and possessing pharmacological properties similar to those of morphine, have been described. At least three separate families of peptides have opioid properties (Table 24.2), and the different classes of pep-tides reside in separate distinct neurons. It is likely that the endogenous opioid peptides coexist in neurons with other nonopioid neurotransmitters. The initial hope that these endogenous agents or synthetic derivatives of them would be found to retain the analgesic activity of the opioids but be devoid of respiratory depression and/or addictive properties has now somewhat abated.

1Goldstein A. Opioid peptides (endorphins) in pituitary and brain. Science 1976;193:1081-1086.

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