Heroin-like compounds

Another synthetic heroin-like compound was sold to heroin-dependent individuals in California in 1982 as "new heroin", which was soon recognized to cause severe Parkinsonian symptoms in young people. Eventually it was discovered that "new heroin" contained pethidine together with an N-methyl-phenyl-tetrahydropyridine (MPTP) contaminant. It is now established that MPTP is converted to a neurotoxic... 

As it can be observed in Fig. 2, three out of the 16 investigated compounds, namely, heroin, lysergic acid diethylamide (LSD), and its metabolite 2-oxo, 3-hydroxy-LSD (O-H-LSD), were not detected in any wastewater sample. Two other target analytes, 6-acetyl morphine (6ACM) and A9-tetrahydrocannabinol (THC), were only present in influent wastewaters and with low detection frequencies. The most ubiquitous compounds, present in all influent and effluent wastewater samples analyzed, were the cocaine metabolite benzoylecgonine, and the amphetamine-like compounds ephedrine (EPH) and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Cocaine, cocaethylene (CE, transesterification product of cocaine formed after the joint consumption of cocaine and ethanol), and morphine (MOR) were detected in all influent, but not in all effluent wastewaters (see Fig. 2). 

The consumption indicator is the metabolic byproduct excreted at the highest rate. It may be a metabolite, as it is the case for cocaine (BE) and heroin (MOR), or the drug itself, as it is the case of amphetamine-like compounds. THC, the most psychoactive cannabinoid of the cannabis herb, is highly metabolized before excretion, thus, the consumption indicator selected (THC-COOH) presents an excretion rate of 0.6%. Despite the fact that OH-THC presents a slightly higher excretion rate (2%), this analyte was not selected to back calculate cannabis use due... 

Minor Drugs of Abuse Heroin and Amphetamine-Like Compounds. 447... 

Heroin and amphetamine-like compounds (amphetamine, methamphetamine, MDMA or ecstasy, (R,R)(—)-pseudoephedrine (PS-EPH), and (lS,2R)(+)-ephed-rine hydrochloride (EPH-HCl), the last two measured together as total ephedrine) have so far only been detected in airborne particulates in Spain (Tables 5, 6 and 7). Mean heroin concentrations ranged between 10 and 50 pg/m (Table 5), with maximum daily levels reaching 80-90 pg/m. The maximum concentrations were detected in Madrid and A Coruna, and seemed to be independent of population size. As for amphetamine-like compounds, airborne levels were always below 15 pg/m ... 

Opioid refers to any compound that acts like morphine, the most abundant alkaloid compound in opium. The term opioid includes substances that are derived from plants (such as morphine and codeine), those that occur naturally in the body (such as endorphins and enkephalins), and synthesized compounds (such as heroin and fentanyl). [Endorphins and enkephalins are discussed in Chapters 2 and 3. Fen-tanyi is discussed in Chapter 3.]... 

Subsequent conversion into heroin 2 was first reported in 1874 by Wright in the UK as a result of boiling morphine acetate the process was commercialised by Bayer AG in 1898. The subsequent use and abuse of these compounds is much too complex to discuss here, but one major discovery came in the early 1970s when Pert and Synder reported the identification of opioid receptors in brain tissue.17 This report was followed closely by the identification of endogenous morphine-like substances in 1975 by Kosterlitz and Hughes,18 which over the next few years led to the identification of enkephalins, endorphins and dynorphins—all of which had the common N-terminal sequence of Tyr-Gly-Gly-Phe-(Met/Leu), leading to the concept that morphine actually mimics this sequence.19... 

Drugs derived from morphine and other opium compounds are called opiates. Today, many hundreds of opiates are known some are semisynthetic derivatives, like heroin, and others are purely synthetic, like Demerol. In general, all of the opiates produce similar effects. They differ from each other in potency, in duration of action, in how active they are by mouth, and in how much mood change they cause relative to their physical effects. Opiates that arc more potent, shorter-acting, and more active by injection lend themselves more easily to abuse. 

Opiates are compounds extracted from the milky latex contained in the unripe seed pods of the opium poppy (Papaver somniferum). Opium, morphine, and codeine are the most important opiate alkaloids found in the opium poppy. Opium was used as folk medicine for hundreds, perhaps thousands of years. In the seventeenth century opium smoking led to major addiction problems. In the first decade of the nineteenth century, morphine was isolated from opium. About 20 years later, codeine, one-fifth as strong as morphine, was isolated from both opium and morphine. In 1898, heroin, an extremely potent and addictive derivative of morphine was isolated. The invention of the hypodermic needle during the mid-nineteenth century allowed opiates to be delivered directly into the blood stream, which increases the effects of these drugs. Synthetically produced drugs with morphine-like properties are called opioids. The terms narcotic, opiate, and opioid are frequently used interchangeably. Some common synthetically produced opioids include meperidine (its trade name is Demerol) and methadone, a drug often used to treat heroin addiction. 

Hundreds of morphine-like molecules have been synthesized and tested for their analgesic properties. Research has shown that not all the complex framework of morphine is necessary for biological activity. According to the morphine rule, biological activity requires (1) an aromatic ring attached to (2) a quaternary carbon atom and (3) a tertiary amine situated (4) two carbon atoms farther away. Meperidine (Demerol), a widely used analgesic, and methadone, a substance used in the treatment of heroin addiction, are two compounds that fit the morphine rule. 

In 1874, British chemist Alder Wright published reports of experiments that produced a new chemical compound based on an alteration of morphine diacetylmorphine. Wright s discovery went unnoticed until 1898, when the great German pharmacologist Heinrich Dreser (who also discovered aspirin see Chapter 14) rediscovered the compound and noted that it was twice as potent as morphine. Because this new compound was so powerful, it was viewed as a new treatment with heroic possibilities and was christened heroin. Heroin was used immediately as a cough suppressant and pain reliever. Not until many years later was it recognized that heroin was even more likely than morphine to produce dependence. 

Diamorphine (or heroin) is the diacetyl derivative of morphine and, like morphine, is used as a narcotic analgesic (Figure 8.21). The two acetyl groups are important for two reasons first, they render the molecule more lipophilic (increasing the partition coefficient), which means that diamorphine is absorbed into the central nervous system more rapidly than is morphine, and in turn results in a faster onset of action than for morphine (and, sadly, makes the compound a favourite with addicts). The second aspect of the two acetyl groups is that they are susceptible to hydrolysis, to yield morphine and two molecules of acetic acid (Figure 8.21). 

The analgesic methadone (Fig. 12.25) was discovered in Germany during the Second World War and has proved to be a useful agent comparable in activity to morphine. Unfortunately, methadone retains morphine-like side-effects. However, it is orally active and has less severe emetic and constipation effects. Side-effects such as sedation, euphoria, and withdrawal are also less severe and therefore the compound has been given to drug addicts as a substitute for morphine (or heroin) in order to wean them... 

Many researchers are working to understand why drugs like morphine and heroin are addictive. Studies with cells in culture have suggested one mechanism for morphine tolerance and addiction. Normally, when the cell receptors bind to enkephalins, this signals the cell to decrease the production of a chemical messenger called cyclic AMP, or simply cAMP. (This compound is very closely related to the nucleotide adenosine-5 -monophosphate.) The decrease in cAMP level helps to block pain and elevate one s mood. When morphine is apphed to these cells they initially respond by decreasing cAMP levels. However, with chronic use of morphine the cells become... 

Cocaine metabolites were detected in nrine by solid phase extraction (SPE) IMS with detection limits of 10 and 4 ng/mL for BE and cocaethylene, respectively. The analytes are retained on the SPE cartridge, while salts and polar compounds that may interfere with the analysis remain in solntion. Sweat samples have also been examined by ion trap mobility spectrometry (ITMS), and traces of 6-acetylmorphine, heroin, and cocaine were detected. Not only illicit drugs can be detected by IMS, but also food additives or supplements that are undeclared, like the appetite suppressant sibutramine. ... 

Fentanyl, a synthetic chemical compound, was discovered to be about 100 times as potent as morphine or heroin. Its chemical structure shown in Fig. 17.11 indicates that it can also be classified as an alkaloid. This compound has been widely used as an anesthetic in surgical procedures, as the physiological effects are much shorter-acting than morphine. And it gives a high like heroin, though short-lived. 

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