Morphine drug action

I o find new and more effective medicines, chemists use various models that J. describe how drugs work. By far, one of the most useful models of drug action is the lock-and-key model. The basis of this model is the connection between a drugs chemical structure and its biological effect. For example, morphine and all related pain-relieving opioids, such as codeine and heroin, have the T-shaped structure shown in Figure 14.1. 

The demonstration of the existence of strictly defined SARs. which is perhaps Ihe most important criterion of drug action at a specific receptor site, has made possible the most important pharmacologic discoveries. For example, the analgesic actions of morphine and related agents, which are indicative of specific receptors, led to die discovery of endogenous opiate peptides, i.e., the leucine and methionine enkephalins and endorphins. 

Unfortunately, to feel pain is an essential condition for survival. Pain-initiated avoidance behavior protects the individual. Morphine, obtained from opium, from the juice of the opium poppy (Papaver somniferum), has been known for millennia to alleviate pain. As mentioned in Chapter 5, endogenous opioids have also been identified. The word opioid is now used to refer to all drugs with morphine-like actions. The structure of morphine is shown in Figure 11.11. Diacetylmorphine (heroin) is made by acetylation at the 3 and 6 positions. 

Finally and probably most important can be the contribution made by such drugs in further pharmacological research. Contrasting compounds such as morphine and WIN 20,228, which are so similar except for their addiction liability, may provide another tool as valuable as nalorphine for further exploration of the problems of analgesia, physical dependence, tolerance, and the relationship between molecular modification and drug action. 

Opioids are drugs that have morphine-like actions and the name comes from the source of morphine and opium, the opium poppy, Papaver somniferum. Opium itself is a mixture of substances that occur in the sap of the opium poppy. 

Unlike morphine, the action of enkephalins is short-lived. They bind to the cellular receptor and thereby induce the cells to respond. Then they are quickly destroyed by enzymes in the brain that hydrolyze the peptide bonds of the enkephalin. Once destroyed, they are no longer able to elicit a cellular response. Morphine and heroin bind to these same receptors and induce the cells to respond. However, these drugs are not destroyed and therefore persist in the brain for long periods at concentrations high enough to continue to cause biological effects. 

These early observations on the correlation of structure and pharmacological action in the morphine group have been greatly extended as a result of chemical, pharmacological and clinical work done under the auspices of the American National Committee on Drug Addiction. In addition to numerous papers, contributed by experts serving this Committee, to chemical and pharmacological journals, two important reports have been published —... 

Narcotic antagonist. A drug that selectively blocks the actions of morphine-like compounds. 

In the strict sense, opiates are drugs which are derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non-peptidic structures. The old term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, pqrtidic or non-peptidic, that produces morphine-like effects through an action on opioid receptors. 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

The term opioid refers to any exogenous substance that acts as an agonist at any of several receptors. Opioid antagonists are drugs that bind to a receptor but produce no actions. The poppy plant, Papaver somniferum, from which opium is obtained, is grown in many areas of the world. Morphine constitutes 10% of opium, and codeine can be obtained direcdy from opium. Semisynthetic opioids such as heroin and oxycodone are obtained directly or indirectly from morphine. There are other distinct chemical classes of drugs with opioid actions, including the methadones. 

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