Morphine chemical structure

Figure 7.3 The chemical structure of fentanyl and its illegal analogues alpha-methyl-fentanyl and 3-methyl-fentanyl are shown here. Fentanyl was originally designed and marketed as an anesthetic, as it is 100 times stronger than morphine.

Figure 7.4 The chemical structure of meperidine, its analogue MPPP, and the closely related neurotoxin MPTP, are all shown here. Meperidine, an anesthetic, was also used as an alternative to morphine. It proved advantageous because it has a shorter length of duration and fewer side effects than morphine.

The chemical structures and biological activities of hundreds of opioid analgesics derived from the prototype opioid drug morphine are most comprehensively described in two books published in 1986, one entitled Opioid Analgesics, Chemistry and Receptors by Casy and Parfitt [1] and the other entitled Opiates by Lenz et al. [2]. Follow-up articles include those by Casy in 1989, entitled Opioid Receptors and their Ligands Recent Developments [3] which also includes sections on opioid peptides, affinity labelling and opioid receptor subtypes Rees and Hunter in 1990 [4] covering the... 

U-50488 has not only been a useful biological lead - its chemical structure, which is apparently unrelated to any of the classical morphine derivatives, has been used as the starting point for several drug discovery programmes. This has led to several publications and patents, particularly during the period 1989-1990, and these are discussed in this section. 

The addictiveness of a given substance goes beyond the chemical structure of the addictive drug itself (i.e., morphine, cocaine, or nicotine). The effects are also related to the dose and speed of delivery, as well as to other substances that might be part of the formulation. For example, just as the oral consumption of opioids and cocaine produce substantially less pronounced behavioral and physiological effects than intravenous or smoked consumption, slow release forms of nicotine produce generally less pronounced effects than smoked forms (Henningfield and Keenan 1993). Similarly, the free base or unprotonated forms of cocaine and... 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

There are many legal medicines that use opiates or opiate-like substances. Most of the opiate-based medicines used today are not made from natural opiates, but are either synthetic or semi-synthetic. Synthetic opiate drugs are not actually opiates at all they are merely different chemicals that act like opiates. Semi-synthetics are those drugs that involve changing the chemical structure of a natural opiate. An example of this is heroin, which is a human-made variation of morphine. Morphine and codeine are the principal natural opiates used as medicines and what follows are descriptions of the other most frequently used opiate-based medicines. 

Figure 7.3 Chemical structure of morphine and allied opioids.

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. 

In the early days of chemistry, when few pure substances were known, newly discovered compounds were often given fanciful names—morphine, quicklime, muriatic add, and barbituric acid (named by its discoverer in honor of his friend Barbara)—to cite a few. Today, with more than 20 million pure compounds known, there would be chaos unless a systematic method for naming compounds were used. Every chemical compound must be given a name that not only defines it uniquely but also allows chemists (and computers) to know the compound s chemical structure. 

Many substances of widely different chemical structure abolish the excitability of nerve fibers on local application in concentrations that do not cause permanent injury and that may not affect other tissues. Sensory nerve fibers are most susceptible, so that these agents produce a selective sensory paralysis, which is utilized especially to suppress the pain of surgical operation. This property was first discovered in cocaine, but because of its toxicity and addiction liability, it has been largely displaced by synthetic chemicals. The oldest of these, procaine (novocaine), is still the most widely used. Its relatively low toxicity renders it especially useful for injections, but it is not readily absorbed from intact mucous membranes and is therefore not very effective for them. Many of its chemical derivatives are also used. They differ in penetration, toxicity, irritation, and local injury as well as in duration of action and potency. Absolute potency is not so important for practical use as is its balance with the other qualities. If cocaine is absorbed in sufficient quantity, it produces complex systemic actions, involving stimulation and paralysis of various parts of the CNS. These are mainly of toxicological and scientific interest. Its continued use leads to the formation of a habit, resembling morphinism. This is not the case with the other local anesthetics. 

Oxycodone is available alone or in combination with either acetaminophen or aspirin. Its chemical structure is most closely related to codeine, but it has strong painkilling effects equal to those of morphine. 

Figure 15.3. Chemical structure of some non-morphine-type opiates.

In 1803 Friedrich Sertumer isolated morphine from opium, but the chemical structure (Fig. 1) was identified by Gulland and Robinson in 1925 and then confirmed by X-ray analysis in 1952 by Gates and Tschudi [8], Only the l isomer is psychoactive, while the d form is totally inactive. It has low solubility in water and high solubility in organic solvents. 

The gold standard of opiate pain relievers is morphine. It was one of the first compounds extracted, isolated, and purified from the opium poppy, and it continues to be one of the most widely used pain relievers today. Morphine and other opiate drugs such as heroin, codeine, oxycodone, and hydrocodone have very similar chemical structures (Figure 3.2). However, other opiates such as fentanyl and meperidine (Demerol) have a slightly different structure (Figure 3.3). 

Figure 3.2 This diagram illustrates the chemical structures of morphine, codeine, oxycodone, hydrocodone, and heroin. Notice how each molecule differs from the others by only a few atoms.

Modification of the chemical structure of natural substances has frequently led to pharmaceuticals with enhanced potency. An illustrative example is fentanyl, which acts like morphine but requires a dose only 0.1-0.05 times that of the parent substance. Derivatives of fentanyl such as carfentanyl (employed in veterinary anesthesia of large animals) are actually 5000 times more potent than morphine. 

In the 1970s, Hughes et al. were the first to show that two very different chemical structures have similar agonist properties (3). The opioid natural product, morphine (3), was found to resemble the N-terminal structure of the endogenous opioid peptides, enkephalins, (4a) and (4b), and j3-endorphin (5) (Fig. 15.2). The remarkable similarity between the morphine phenol system and the IV-terminal tyrosine residue in the peptide opioids implied that these units reacted with opioid receptors in a similar fashion to elicit comparable responses (4-6). 

Finally, several molecules with chemical structures similar to morphine have been found in mammalian brain, but it is not certain if these molecules have been derived from dietary sources or if they are synthesized in the brain. 

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