Ephedra - Ephedrine

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. 

The world war made all these sources of supply difficult of access and stimulated interest in the possibilities of local production. Examination of a number of American species of ephedra had already shown them to be devoid of alkaloids, except for the S. American species E. andina, in which Chavezt found ephedrine, and in the United States attention has been given to the experimental cultivation of imported species, notably E. sinica and E. gerardiana a Moroccan type, E. alenda, was found to contain only ). In Australia experimental cultivation of the Indian species E. gerardiana, E. intermedia and E. nebrodensis has been tried and preliminary yields of 1-35, 1-OS and 0-98 per cent, of total alkaloids respectively have been recorded. In Russia, E. equisetina and E. intermedia are available and are considered to be worth exploitation. In Italy various local species have been found to contain mainly i -ephedrine and that in small amount, but better results are recorded for two species already referred to and which are available in Sardinia, viz. E. vulgaris Rich and E. nebrodensis. ... 

To avoid the difficulty of variation in alkaloidal content liable to occur in commercial Ephedra a proposal.has been made in India for the manufacture of a standardised extract representing 5 per cent, of the weight of the crude drug and containing 18 to 20 per cent, of the total alkaloids. Both in India and China experimental extraction of ephedrine has been started. ... 

The total alkaloidal eontent of Ephedra varies widely, being influeneed by the speeies eolleeted and the seasonal and environmental eonditions, as has been shown by Read and by Chopra and their eolleagues. For speeially eolleeted material yields as high as 2- 56 per cent., of which 1- 8 per cent, is ephedrine, have been recorded, but about 1 per cent, of total alkaloids is not usually exceeded in the commercial product. 

For commercial Ephedra the British Pharmaceutical Codex, 1934, specifies a total alkaloidal content of not less than 1-25 per cent, when assayed by the method therein prescribed. The proportion of Z-ephedrine is generally about 70 per cent. Methods of assay for total alkaloids are described by Feng and Read and by Krishna and Chose, who discuss the various difficulties involved and comments on these and other methods have been made by various workers. Conditions affecting the results of such assays have also been discussed by T ang and Wang, and Brownlee has shown that chloroform is not a suitable medium for the assay since it converts ephedrine quickly and 0-ephedrine slowly to the hydrochloride. 

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

Ephedrine is the principal active ingredient in the herb ephedra, or ma huang. It is similar in form to the appetite-control drug phenylpropanolamine (banned in the United States), which is also known as norephedrine, meaning ephedrine whose methyl group has been replaced by a hydrogen. 

Ephedrine and pseudoephediine are a vasodilator and decongestant respectively used widely in the treatment of asthma and the symptoms of colds and influenza. These pharmaceuticals were derived originally fi om the plant Ephedra sinica and used in traditional Chinese medicinal preparations. Although some are still produced fi om such sources, the major production is via a fermentation process followed by a chemical catalytic reaction. As shown in Figure 1, the intermediate / -phenylacetylcarbinol (PAC) is produced by decarboxylation of pyruvate followed by ligation to benzaldehyde. 

Ma Huang (Ephedra sinica) is another potentially harmful herb that is available in the United States. Claims of utility of Ma Huang for the treatment of bronchial asthma, cold and flu symptoms, fevers or chills, headaches and other aches, edema, and lack of perspiration have been made [23], Ma Huang contains approximately 1% of ephedrine and therefore possesses central nervous stimulatory potential [24], However, ephedrine is difficult to extract and purify from Ma Huang, so it presently has no street value. 

Ephedra, also known as Ma-Huang, is a central nervous system stimulant that is similar to amphetamine. Ephedra alkaloids (a material found in plants) with the active ingredient ephedrine have been used for medicinal purposes in China for... 

Kim J and Choi YH. 2000. SPE of ephedrine derivates from Ephedra sinica. Proceedings of 5th International Symposium on Supercritical Fluids, Atlanta, GA, pp. 1—12. 

The Mormons were introduced to ephedra by Indians when they arrived in Utah. They used it as an alternate to tea and coffee, ironically, because their religious views prohibited use of those stimulants. Ephedra might be the oldest known human stimulant, because remains of the plant were discovered in a fifty thousand-year-old Neanderthal grave in Iraq. Modern medical use of ephedra began with the identification of the alkaloid ephedrine in 1923. 

Several alkaloids are present in Ephedra, with ephedrine being the most significant (Gruenwald et al. 1998). Ephedra sinica contains approxi-... 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

Normal doses range from 15 to 30 mg of actual alkaloid (ephedrine), and the lethal dose is in the 1-2 g range. Side effects from ephedra use include headache, irritability, restlessness, anxiety, insomnia, tachycardia, urinary disorders, and vomiting. 

Other conditions in which ephedra is contraindicated are anxiety disorders, angle-closure glaucoma, prostate adenoma with residual urine volume, pheochromocytoma, and thyrotoxicosis (Gruenwald et al. 1998). Known medications that may interact adversely with ephedrine include heart glycosides, halothane, guanethidine, MAO inhibitors, secale alkaloids, and oxytocin. 

The principal active ingredient in ephedra is ephedrine. Synthetically produced ephedrine has been approved by the FDA for use as a drug. Under those more controlled conditions, the compound has not been associated with any adverse events of the kind reported for the natural product. 

Ephedrine is an alkaloid that is present in various forms of the ephedrine family, and which is still extracted from Ephedra sinica and Ephedra equisetina. Because of the presence of two asymmetric atoms, there are four isomeric forms. Pseudoepinephrine (d-isoephrine) is a stereoisomer with pharmacological action that differs slightly from ephedrine. The pharmacological action of ephedrine is typical of noncatecholamine sympathomimetics of mixed action. It stimulates both a- and 8-adrenoreceptors, and simultaneously causes a release of norepinephrine from synaptic neurons. Its vasoconstrictive ability is approximately 100 times weaker than that of epinephrine however, the duration of action is approximately 10 times longer. It is much less toxic than epinephrine, which allows it to be used widely in medicine. 

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