Ephedrine market

Indeed, PDC catalyzes mainly the reaction of pyruvate with benzaldehyde for the formation of (R)-PAC 27. This C—C bond formation, a two-carbon unit elongation, is coupled to the concomitant decarboxylation of pyruvate 26. This reaction is industrially developed for the synthesis of (—)-ephedrine by adding a second step, a reductive amination. Ephedrine (marketed by Merck especially) is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, and decongestant, and it is used to treat hypotension associated with anesthesia. It is similar in structure to the (semisynthetic) derivatives amphetamine and meth-amphetamine. Chemically, it is an alkaloid derived from various plants in the genus Ephedra (family Ephedra-ceae). It works mainly by increasing the activity of noradrenaline on adrenergic receptors. ... 

Many diet pills that work by increasing the number of calories burned have been developed. Most of these contain one or more of the three ingredients caffeine, phenylpropanolamine (PPA), and ephedrine. In the United States, PPA and ephedrine have been withdrawn from the market because they produce serious side effects, including heart attack and stroke. Caffeine, which is still found in many diet pills, will be further discussed in Chapter 6. 

Considering that the consumption pattern observed in the area of the Ebro River basin studied, which covers about half of the population living in the basin, could be representative of the whole Spanish country, the estimated average consumption data were used to calculate the annual consumption of each drug in the whole basin and in the Spanish territory. According to the extrapolated figures, which are shown in Table 2, around 21 tons of cocaine, 8 tons of cannabis, 3 tons of amphetamine and ephedrine, 300 kg of ecstasy and heroin, and 7.5 kg of methamphetamine are annually consumed in Spain. These amounts would move in the black market for around 1,100 million Euros. 

FDA. 1996. Additional Market Review Information. Briefing Materials for Food Advisory Committee on Dietary Supplements Containing Ephedrine Alkaloids. Food and Drug Administration. Center for Food Safety and Applied Nutrition, USA. 35pp. 

L-Ephedrine is a well accepted and widely used drag so that markets are significant. 

Ephedra (ma huang) is a popular botanical incorporated into a variety of formulations for weight loss, energy or performance enhancement, and symptomatic control of asthma. A pharmacodynamic interaction leading to a fatality has been reported with concurrent use of caffeine and ephedra (62), possibly as a result of additive adrenergic agonist effect of the ephedrine alkaloids and caffeine on the cardiovascular system and the CNS (63). Ephedra was recently withdrawn from the market (64). 

Role of Project PRISM in countering synthetic drugs and their precursors , INCB presentation to the Conference Europe-Asia Cooperation on Synthetic Drugs and their Precursors , Paris, 6-7 March 2007. These are substantial amounts. By comparison, total licit trade in ephedrine and pseudo-ephedrine is estimated at around 30 mt and 1,200 mt respectively. [Source INCB, 2005 Precursors]. The 16 mt of interdicted/suspended shipments could have been used to produce 110 mt of methamphetamine. Were this to have ended up on the illicit market, it would have increased global methamphetamine production by some 40 per cent. 

Ephedrine was a popular ingredient in many diet pills and muscle and energy boosters for decades. Ephedrine-based products were marketed to teenagers and young adults as having the ability to produce euphoria (feelings of pleasure) and increased sexual sensations, energy, and alertness. However, over the last decade, scientists have linked ephedrine use to numerous heart attacks, strokes, and deaths. 

The abuse of marketed medications has been at the forefront of public awareness in recent years, mostly due to widespread reports concerning OxyContin and hydrocodone.1 While these are highly regulated, prescription-only medications with recognized potential for abuse, even some over-the-counter (OTC) medications have become problematic, either because of their own effects (e.g., ephedrine) or because they are used in the manufacture of other abused substances (e.g., pseudoephedrine, used to make methamphetamine).2 3... 

Interest in ephedrine in Western medicine was created by the classical investigations of Chen and Schmidt, which began in 1923 as a result of a Chinese druggist s assurance that ma huang was really a potent drug. These workers reported the cardiovascular effects of the alkaloid, its similarity to epinephrine, and its absorption from the intestinal tract. Numerous clinical and experimental studies soon followed, and the use of ephedrine spread so rapidly that several tons of the alkaloid are now consumed yearly. Synthetic ephedrine (racemic) was first prepared in 1927 and marketed under the name Ephetonin (Goodman and Gilman, 1955). 

In the 1990s, methcathinone—called by various street names such as cat, goob, Jeff, speed, bathtub speed, mulka, gaggers, the C, wild cat, Cadillac express, and ephedrine—appeared as a drug of abuse on the black market. Methcathinone, a synthetic form of cathinone, is an even more potent stimulant than its natural counterpart and is illegal in the United States. 

Dextromethorphan is sold alone or, when mixed with other drugs such as phenylpropanolamine or ephedrine, is marketed as ecstasy, after the widely abused street drag. Of course, this formulation is not the same compound as ecstasy. It has also been used to deceive persons who are seeking to buy narcotics such as heroin. The greatest amount of dextromethorphan abuse so far has occurred with the over-the-counter cough formulas. Reportedly, dextromethorphan is also being sold on the Internet in pill and capsule forms as well as the powder. 

Ephedra is available in multiple forms. It is a common ingredient in energy boosting bars, sold as Herbal Ecstasy in some health food stores, and is also available as powder that can be mixed with water. Health food stores may sell powdered ephedrine stems, which can be used in a tea, or they may sell infusion, extracts, tinctures, or tablets of ephedra. Health food stores may also sell ephedra as the ma huang herb. Many manufacturers tend to advertise or market ephedra supplements as natural or as a botanical herb, because some consumers equate natural with safe. In China, ephedra may be boiled with cinnamon twig, licorice root, and almond to treat the common cold. 

In New Zealand, herbal ecstasy is a term used for many different herbal formulations, none of which contains ecstasy. Some of the names for these herbs (which can be sold in stores) include The Bomb , Reds , and Sublime . Analysis of The Bomb showed substantial amounts of ephedrine the Ministry of Health in New Zealand removed it from the market. Some symptoms associated with herbal ecstasy include headache, dizziness, palpitation, tachycardia, and raised blood pressure. Thus, in countries where the term herbal ecstasy is commonly used, it is important that those who see patients who have taken herbal ecstasy should not confuse it with ecstasy, as toxicity and medical management may be quite different (133). 

On October 3, 1996, President Clinton signed into law the Comprehensive Methamphetamine Control Act of 1996 (MCA). The MCA broadens controls on listed chemicals used in the production of methamphetamine, increases penalties for the trafficking and manufacture of methamphetamine and listed chemicals, and expands controls to include the distribution of lawfully marketed drug products which contain the listed chemicals ephedrine, pseudoephedrine and phenyl-propanolamine (PPA). 

A number of plant species from the genus Ephedra have been used for many years for their stimulant effects. Ephedra sinica is native to Asia and is frequently sold under its Chinese name, ma huanpf. Another species, E. nevadensis, grows in the American West and is known as Mormon tea. The main psychoactive compound in ephedra is ephedrine. Ephedrine is a potent stimulant with effects much like those reviewed in Chapter 6. It is sympathomimetic and produces behavioral effects similar to those of other stimulants (Karch, 2000). Until 2004, ephedrine products were marketed through stores or by mail order to increase energy, prevent drowsiness, suppress appetite, and in high-dose formulations, as an herbal alternative to ecstasy (see Chapter 12). These products contained a wide variety of plant products and... 

Ephedrine is labeled for sale as a bronchodilator. Caffeine is marketed as a minor stimulant to produce greater alertness or reduce drowsiness. Synephrine is available from plant sources as an herbal weight loss supplement. 

Speed is the nomenclature used for a number of preparations that resemble and are often misrepresented as prescription amphetamines. They are used as substitutes for amphetamines. Speed is commonly composed of ephedrine, caffeine, synephrine, or a combination of these agents. Ephedrine is probably the most frequently encountered component of street speed. Elerbal weight loss products containing ephedra, which is made up a number of sympathomimetic alkaloids, were removed from the US market in 2003. Phenypropanolamine, previously marketed as a weight loss supplement and oral decongestant and abused as a look alike , was removed from the US market in 2002. 

All ephedra plants contain phenylalanine-derived alkaloids, including ephedrine, pseu-doephedrine, methylephedrine, and trace amounts of phenylpropanolamine. Previously marketed herbal supplements typically stated total ephedra alkaloid content, although actual levels of individual alkaloid varied depending on raw material and production runs. 

Ephedra was also sold in combination with many other herbs in obscure combinations. Labels frequently listed 10 or 15 different herbs, but, analysis usually disclosed only the ephedra alkaloids and caffeine as present in sufficient quantities to be physiologically active. After several well-publicized accidental deaths, products clearly intended for abuse, such as herbal ecstasy, and other look-alike drugs (products usually containing ephedrine or phenylpropanolamine designed to look like illicit methamphetamine, but in concentrations higher than recommended by industry or the FDA) were withdrawn from the market. Labels on these products were frequently misleading. For example, one might suppose that a product called Ephedrine 60 contained 60 mg of ephedrine when, in fact, the actual ephedrine content was 25 mg. 

Amphetamine was the first anorectic drug to be introduced into clinical practice. It was originally synthesised in the 1920 s as a potential substitute for ephedrine and marketed under the trade name of Benzedrine for use as a nasal decongestant. Initially, it was thought to have very little, if any, effect on the central nervous system. However, within a relatively short time it was noted that, in contrast to what had first been thought, amphetamine had pronounced stimulant and mood elevating properties. 

A drug product that contains the same active constituent as a botanical product would be regulated according to different paths, as long as they are marketed with different intent. The combination of caffeine with any other stimulant, such as ephedrine alkaloids2, may not be sold as an OTC drag product (20). However, dietary supplement products that contain ma huang (a source of ephedrine) and natural product stimulants such as kola nut (50% caffeine) are permitted on the market under DSHEA. 

Phenylpropanolamine (PPA). Until recently, PPA was widely available in a number of nonprescription cold medications and diet control products. Adverse effects are similar to those described for ephedrine. In response to an FDA warning of increased risk of hemorrhagic stroke, especially in women, PPA has been withdrawn from the market by most manufacturers. Before this withdrawal, PPA was another popular starting product for synthesis of S(-f-)-methamphetamine. PPA is also a metabolite of ephedrine and pseudoephedrine. 

Herbal substitutes for dru [s of abuse A variety of herbal mixtures are offered for sale in magazines, on the internet and in so-called smart , eco or head shops. Many are marketed as herbal Ecstasy and the plants included in the formulations include Yohimbe bark, Kava-Kava (Piper methysticum),Y-3 e.emi, Hops, Jaborandi and Alisma. One product contains Kava-Kava, Guarana, Uva Ursi and Cascara bark. Many of the products sold as herbal Ecstasy contain either Ephedra sinica (Ma huang) or the Indian plant Sida cordifolia which both contain the alkaloid ephedrine (see R03c, Chapter VI). Other alkaloids may also occur, such as pseudoephedrine, norephedrine and norpseudoephedrine. The side-effects of ephedrine include tachycardia, anxiety, insomnia and arrythmias and a hypotensive crisis may develop if monamine oxidase inhibitors are also taken. Many adverse reactions and more than 20 deaths have been attributed to ephedrine and Ephedra consumption. Research conducted in the US shows that the daily intake of some Ephedra products would give ephedrine levels well above the recommended therapeutic doses. 

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