Morphine is one of the 20 alkaloid substances, present in a typical yield of 10% of raw opium. Morphine was first isolated in 1805 by Friedrich Sertürner, an apothecary's assistant in Paderborn, Germany, however its basic structure was not correctly determined until 120 years later. In the 1800s morphine (known then as laudanum) was a popular panacea and was available from grocers and markets. Later on its addictive qualities led to its use and availability being severely restricted.
Morphine is isolated from opium in large quantities (over 1000 tons per year), although most commercial opium is converted into codeine by methylation. Morphine acts as an anesthetic without decreasing consciousness, and it is one of the most powerful analgesics known. However it also suppresses the respiratory system, and high doses can cause death by respiratory failure. Its analgesic properties are related to the ability of the molecule to fit into and block a specific receptor site on a nerve cell. This eliminates the action of the pain receptor, preventing the pain signals reaching the brain. This is similar to the way in which the body's natural painkillers (endorphins and enkaphalins) work. The shape of the morphine molecule is crucial to its ability to exactly fit into the active site on the receptor - the 'lock-and-key' mechanism. The benzene group of the morphine molecule fits snugly against a flat section of the receptor protein, whilst the bent neighbouring group of carbon atoms fits into a nearby groove. This allows the positively charged nitrogen atom to attach to a negatively-charged group on the receptor, so locking the two molecules together.
Morphine blocks deep aching pain, but has no effect on the fast pain that results from injury. One side effect of the analgesic action is that the patient often gets a feeling of detachment from the world, along with euphoria and sometimes pleasure. It is this which makes morphine, and the other drugs related to it (such as heroin), attractive to those who want to use drugs for 'recreational' reasons. However all of these drugs are highly addictive, and the body rapidly gets acclimatised to their use, such that increasingly large dosages are required for the same effect.
Morphine - replacing the -OH group shown in red with -OCH3 produces codeine. Replacing the both the red and blue -OH groups with OCOCH3 produces heroin.
Codeine - the methoxy addition is shown in red.
Pethidine - the parts of the molecule resembling the morphine structure are shown in red.
The isolation of morphine was the beginning of alkaloid chemistry, which has yielded many important medicinal substances. Although a satisfactory theory of analgesic structure or action still eludes us, experimenters have developed a number of synthetic analgesics related to morphine. The oldest is pethidine (also known as meperidine, Demerol and about 40 other names). It was synthesised in 1939 by the German chemist Otto Eisleb. It is less potent than morphine, but is still widely used for the relief of post-operative pain. By replacing one of the -OH groups with a methoxy group, morphine is converted into codeine, another powerful painkiller. When mixed with paracetamol it goes by the trade name Tylenol. When consumed, the -OCH3 group is converted back to -OH and regenerating the morphine again.