Ephedra and ephedrine

Table 2 Federal and State regulatory actions against ephedra and ephedrine-containing alkaloids ...

Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance a meta-analysis. JAMA 2003 289 1537-1545. 

Shekelle, P., Hardy, M., Morton, S., Maglione, M., Mojica, W., Suttorp, M., Rhodes, S., Jungvig, L., and Gagne, J. 2003a. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance A meta-analysis. JAMA 289, 1537-1545. 

They include such compounds as tyramine (p-hydroxyphenylethylamine) from ergot, ephedrine from ephedra, and colchicine from colchicum (Figure 11.1). 

Some body builders tout the combination of caffeine with the herbal stimulant ephedra as harmless, and suggest the combination helps turn fat into muscle. A study published in 2001 does support the claim that caffeine and ephedrine can boost results in laboratory attempts to mimic the tasks of competing athletes. However, ephedra, the herbal drug containing the chemical ephedrine, has been linked to several deaths. 

Ephedra has a long history of legal use in the United States and around the world. Today, the laws that apply to ephedra cover sales, formulation, and labeling by manufacturers they do not outlaw its use by consumers as with street drugs such as marijuana and cocaine. Because ephedrine can be used to manufacture methamphetamine, companies that sell bulk ephedrine and ephedrine tablets are subject to laws... 

The oriental crude drug Ma Huang or Mao, prepared from certain species of the genus Ephedra, contains ephedrine, pseudoephedrine, and homologous compounds (2). Although alkaloids of the ephedrine type occur in several Ephedra species, only a few other plant sources are known (Table IV and V). 

The six optically active alkaloids ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and the N-methylated N-methylephedrine and N-methylpseudoephedrine are described in detail in Reti s review (2). Two new alkaloids of related structure have since been identified in Ephedra species, namely, (9-benzoylpseudoephedrine (271) and the oxazolidine derivative ephe-droxane (272). The 4-quinolone derivative ephedralone, recently isolated from Ephedra alata (273), may be of similar biogenetic origin as the ephedrines. Ephedra species also contain macrocyclic alkaloids of more complex structure (275). The two major Ephedra alkaloids (—)-ephedrine and (+)-pseudoephedrine are diastereomers. (—)-Ephedrine has the erythro and (+)-pseudoephedrine has the threo configuration. 

Many alkaloids have pronounced biological properties, and many of the pharmaceutical agents used today are derived from naturally occurring amines. Morphine and related alkaloids from the opium poppy, for instance, are used for pain relief atropine from the flowering plant Atropa belladonna, commonly called the deadly nightshade, is used as an anti-spasmodic agent for the treatment of colitis and ephedrine from the Chinese p smt Ephedra sinica is used as a bronchodilator and decongestant. 

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... 

Many cases of serious adverse effects and even fatalities have been reported that were linked with ephedra or ephedrine administration over the last 10 years. Haller and Benowitz published a review of 140 reports of adverse events related to the use of ephedra alkaloids that were submitted to the FDA between June 1997 and March 1999. Using standardized rating system for assessing causation, 31% of the cases were considered to be definitely or probably related to the use of ephedra alkaloid-containing supplements, and another 31% were deemed to be possibly related. Among these adverse events, 47% involved in cardiovascular symptoms and 18% involved the CNS. Hypertension was the most frequent adverse effect, followed by palpitations, tachycardia, or both stroke and seizures. Ten events led to death and 13 cases produced permanent disability. 

As with other sympathomimetic agents, theoretical drug interactions with ephedra alkaloids are possible. Despite this potential, only a handful of adverse drug interactions have been reported. This is especially pertinent when considering the extensive use of both ephedra-containing supplements and ephedrine- or pseudoephedrine-containing OTC products. The most notable interaction exists between nonselective monoamine oxidase inhibitors and ephedra- or ephedrine-containing products. 

Of course, this restriction has caused some consternation among herbalists or Chinese practitioners who still believe that within the context of traditional use, Ma Huang has its merits. In Canada, the ephedrine alkaloid is limited to levels well below the excesses seen in U.S. products, a policy that allows the continued sale of traditional Chinese Ephedra products. Canada also allows Ephedra to be included in products used for nasal congestion in the following small doses 8 mg/dose or 32 mg/day of ephedrine and 400 mg/ dose or 1600 mg/day. However, Health Canada has issued several warnings regarding the illegal sale of Ephedra and the potential risks that are involved, particularly when it is combined with caffeine or other stimulants. 

Fundamentally, there are only two ways to treat obesity reduce El and increase EE. Thermogenesis and fat oxidation are to a large extent under the control of the sympathetic nervous system and its neurotransmitter norepinephrine after a rational approach for obesity management. In this context, there has been much interest in the potential thermogenic effects of many compounds extracted from plants, namely, caffeine from coffee and tea, ephedrine from ephedra, and capsaicin from pungent spices, largely because of their potential to modulate catecholamine release and activity. ... 

Several amino alcohols have been isolated from Ephedra species ephedrine (3), norephedrine (1), pseudoephedrine (or t/ -ephedrine, 4), and norpseudoephedrine (2). The pseudocompounds are diastereomers of the corresponding alkaloids. 

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