ABSTRACT
The history of opioids and its receptors span several millennia. The rst evidence of uses of the seed pods of Papaver somniferum dates back to 4200 BC, and numerous ndings and descriptions up through history witness the use of different parts of this plant for food, anesthesia, and ritual purposes. Opium (from opos, the Greek word for juice) refers to the liquid that appears on the unripe seed capsule when it is notched. This liquid contains as much as 16% of morphine, a compound that was isolated already in 1806 as the major active ingredient in opium. A few years later, codeine was also isolated. Morphine can now be produced and applied in its pure form for the treatment of pain and as an adjunct to general anesthetics, but it was quickly realized that morphine had the same potential of abuse as opium. In 1898, heroin was synthesized and claimed to be a safer, more efcacious, nonaddicting opiate as were several other analogs around that time; however, later they all proved to be unsafe. Heroin is an early example of a prodrug since the highly potent analgesic properties can be attributed to the rapid metabolism to 6-monoacetylmorphine and morphine, combined with higher blood-brain barrier penetration due to better lipid solubility compared to morphine (Figure 19.1).
