Synthetic opioids were invented, and biological mechanisms for their actions discovered, in the 20th century.[167] Scientists have searched for non-addictive forms of opioids, but have created stronger ones instead. In England Charles Romley Alder Wright developed hundreds of opiate compounds in his search for a nonaddictive opium derivative. In 1874 he became the first person to synthesize diamorphine (heroin), using a process called acetylation which involvedboiling morphine with acetic anhydride for several hours.[179]
Heroin received little attention until it was independently synthesized by Felix Hoffmann (1868–1946), working for Heinrich Dreser (1860–1924) at Bayer Laboratories.[193] Dreser brought the new drug to market as an analgesic and a cough treatment for tuberculosis, bronchitis, and asthma in 1898. Bayer ceased production in 1913, after heroin's addictive potential was recognized.[179][194][195]
Several semi-synthetic opioids were developed in Germany in the 1910s. The first, oxymorphone, was synthesized from thebaine, an opioid alkaloid in opium poppies, in 1914.[196] Next, Martin Freund and Edmund Speyer developed oxycodone, also from thebaine, at the University of Frankfurt in 1916.[197] In 1920, hydrocodone was prepared by Carl Mannich and Helene Löwenheim, deriving it from codeine. In 1924, hydromorphone was synthesized by adding hydrogen to morphine. Etorphine was synthesized in 1960, from the oripavine in opium poppy straw. Buprenorphine was discovered in 1972.[196]
The first fully synthetic opioid was meperidine (later demerol), found serendipitously by German chemist Otto Eisleb (or Eislib) at IG Farben in 1932.[196] Meperidine was the first opiate to have a structure unrelated to morphine, but with opiate-like properties.[167] Its analgesis effects were discovered by Otto Schaumann in 1939.[196] Gustav Ehrhart and Max Bockmühl, also at IG Farben, built on the work of Eisleb and Schaumann. They developed "Hoechst 10820" (later methadone) around 1937.[198] In 1959 the Belgian physician Paul Janssen developed fentanyl, a synthetic drug with 30 to 50 times the potency of heroin.[179][199] Nearly 150 synthetic opioids are now known.[196]
