Opiate compounds

Table 8.2. Structurally similar opiate compounds and their relative potencies.

In fact, small amounts of morphine, 6-acetylmorphine, codeine, and thebaine, all opiate compounds, have been found in mammalian brain877 878 and have presumably arisen by the same pathway observed in plants (Fig. 25-10). However, there is no cross reactivity between morphine and alcohol in addicted mice,879 and acetaldehyde is probably not the addictive agent. Acetaldehyde is very reactive and may be responsible for much of the damage caused by ethanol.880 At a blood ethanol concentration of 20 mm a person is legally intoxicated, and large amounts of acetaldehyde may be formed and react with many amines, nucleotides, proteins, etc. Ethanol blocks glutamatergic NMDA receptors and... 

Opiates Compounds derived from, or similar in action to, potent analgesic opium alkaloids. 

Thalidomide and metabolites Methylamphetamine and impurities Related opiate compounds (morphine, hydromorphone, nalorphine, codeine, oxycodone, diacetylmorphine) Theophylline, caffeine, sulfanilamide... 

Patent Opiate Compounds, Methods of Making and Methods of Use... 

Lim, J.T., et al.. Separation of related opiate compounds using capillary electrochromatography. Electrophoresis, 21,737, 2000. 

Knockdown agents are a special form of incapacitating agent which rapidly produces an anaesthetic-Uke state following inhalation. There is one substantiated case of such agents being used in the civil setting, namely the 2002 Moscow Theatre incident, where the Russian special forces claimed they used a powerful opiate compound (a fentanyl). Fatalities occurred from respiratory failure and arrest (see Chap. 10). 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

Dmgs, such as opiates, may undergo metabolism both in the intestinal wall and in the fiver (first-pass metabolism). The metabolism may be extensive and considerably reduce the amount of dmg reaching the systemic circulation. Alternatively, the metabolite may be metabofically active and contribute significantly to the action of the parent dmg. Some compounds undergo enterohepatic circulation in which they are secreted into the GI tract in the bile and are subsequently reabsorbed. Enterohepatic circulation prolongs the half-life of a dmg. 

Morphine and related opiates are known to suppress the cough reflex these compounds have thus been used extensively in antitussive preparations. Since this activity is not directly related to the analgesic potency, the ideal agent is one that has much reduced analgesic activity and thus, presumably, lower addiction potential. The weak analgesic codeine (4) is... 

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

The multiplicity of G proteins coupled to opiate receptors may explain how different opiates can bind to the same receptor yet induce different cellular responses. For example, morphine binds to the cloned rat fi receptor expressed in HEK 293, CHO and COS-7 cells and inhibits cAMP accumulation [80-82]. Morphine can be continuously applied to the cells for up to 16 h, and the potency and magnitude of morphine inhibition of adenylyl cyclase does not diminish [80, 81]. In contrast, the opiate sufentanil can bind to the same cloned fi receptor in HEK 293 cells to inhibit cAMP accumulation. However, sufentanil s actions rapidly desensitize [83]. Since both compounds bind to the same receptor, and the fi receptor is the only receptor these drugs can interact with in these cells, the ability of these two full agonists to differentially regulate the fi receptor must be due to their abilities to affect separate adaptive processes in these cells. 

The lack of effect of the mutations on antagonist binding suggests that these compounds bind in a fundamentally different manner to the opiate receptors than do full agonists. Testing of chimeric opiate receptors have further established that agonists and antagonists bind to different domains of the opiate receptors. 

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract. Examples of such receptors include cholinergic and histaminic, dopaminergic, opiate, serotonin, neurokinin (NK), and benzodiazepine receptors. Theoretically, chemotherapeutic agents, their metabolites, or other emetic compounds trigger the process of emesis through stimulation of one or more of these receptors. 

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