Alkaloids ephedrine

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. 

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. 

Starting with two chiral centres, there should, therefore, be four stereoisomers, and this is nicely exemplified by the natural alkaloid (-)-ephedrine, which is employed as a bronchodilator drug and decongestant. Ephedrine is (li ,25)-2-methylamino-l-phenylpropan-l-ol, so has the structure and stereochemistry shown. 

The alkaloids ephedrine, ergotamine, ergometrine and yohimbine are used in many forms. Products like Dorex or Endrine contain ephedrine as their major component. They are used for many purposes, including treating nasal cold symptoms or in bronchial asthma. More than 25 different drugs containing ephedrine have been developed today. 

N.A. Alkaloids, ephedrine, 1-ephedrine, d-pseudoephedrine.106129511 Treat fevers, relieve kidney pain, asthma, nose and lung congestions, hay fever, and as a hypertensive aid. 

Once considered part of the Gnetaceac, Ephedra is now placed in a family of its own. A northern hemisphere genus with some representation in southern South America, Ephedra is the source of the ancient Chinese drug Ma-huang from which the alkaloid ephedrine and its relatives used in modern medicine are obtained. 

Ephedrine occurs in white, rosette, or needle crystals, or as an unctuous mass. It is soluble in water, alcohol, chloroform, ether, and in liquid petrolatum, the latter solution being turbid if the ephedrine is not dry. Ephedrine melts between 34 and 40°C, depending upon the amount of water it contains it contains not more than 0.1% of ash its solutions are alkaline to litmus it readily forms salts with acids and it responds to the usual tests for alkaloids. Ephedrine excites the sympathetic nervous system, depressing smooth and cardiac muscle action, and produces effects similar to those of epinephrine. It produces a rather long-lasting rise of blood pressure and mydriasis and diminishes hyperemia. The alkaloid may be used in 0.5 to 2% oil spray. 

In general, plants do very well in their environments, notwithstanding the omnipresence of a multitude of potential insect herbivores and a number of vertebrate herbivores as well. Some plant species are very insecticidal, as a consequence of their producing a variety of alkaloids including nicotine, piperine, lupine alkaloids, steroidal alkaloids, ephedrine, berberine, strychnine, gramine, and caffeine.37 These biologically active alkaloids also function as deterrents. In terms of families, caffeine is the the most widely distributed alkaloid, a fact that may be... 

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. 

Since there are two possible configurations for an asymmetrically substituted carbon atom, a structure containing n such centres will, in theory, possess 2 stereoisomers. The actual number of stereoisomers that exist may be less than this due to steric effects. Compounds that have the same stereochemistry at one chiral centre but different stereochemistry at the others are known as diastereoisomers (diastereomers) a good example is given by the alkaloids ephedrine and pseudoephedrine. Ephedrine (the (1R, 2S) diastereoisomer) is a natural product isolated from Ephedra (the Ma Huang plant) and known to Chinese medicine for over 3000 years. It was used in the last century for the treatment of asthma. Pseudoephedrine (the (IS, 2S) diastereoisomer) is a decongestant and a constituent of several over-the-counter cold and flu remedies (Figure 4.12). 

Nowadays the Ephedra species are mainly used for extraction of the active ingredient, the alkaloid (-) ephedrine. Not only the classical Chinese species E. sinica Stapf. is used, but mainly the species E.pferardiana. Wall ex. Stapf and E. major Host. =E. nebrodensis Finco), which both grow in India and Pakistan, and E. distachya L., which grows in Southern France. 

The alkaloid ephedrine was isolated in 1885 by the Japanese chemist W.N.Nagai. Two pharmacologists, the Chinese K.K. Chen and the American G.F.Schmidt, showed in the 1920s that ephedrine is a sympathomimetic, i.e. it has an adrenaline-like effect with two important modifications it is much less active, but the effect has a longer... 

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. 

Pinidine and Coniine Nicotiana Alkaloids yV-Methylpelletierine Lycopodium Alkaloids Lyduraceae Alkaloids Pyrrolizidine Group Tropane and Pyrrolidine Alkaloids Quinoline and Acridme Alkaloids Benzodiazepine Alkaloids Tylophora Alkaloids Cactus Alkaloids Ephedrine... 

The Chinese pharmacopoeia is extensive. Some of the active ingredients from Chinese herbs have been used in Western drugs for example, reserpine from Rauwouofia for antihypertensive and emotional and mental control, and the alkaloid ephedrine from Mahuang for the treatment of asthma. 

The analogous cyclocondensation of the alkaloid (-)-ephedrine with urea gives (4i ,55)-l,5-dimethyl-4-phenylimidazolidin-2-one 2. This compound can be used as a chiral auxiliary for asymmetric syntheses [124] ... 

Ionic liquids derived from the alkaloid ephedrine or (S)-valinol have been readily obtained on a kilogram scale in a three-step synthesis a Leuckart-Wallach reaction followed by alkylation with Me2 SO4 and ion exchange in aqueous solution (Scheme... 

Grimbergen, R.F.P. Reedijk, M.F. Meekes, H. Bennema, P. Growth behavior of crystal faces containing symmetry-related connected nets a case study of naphthalene and anthacene. J. Phys. Chem. B 1998, 102, 2646-2653. Strom, C.S. Leusen, F.J.J. Geertman, R.M. Ariaans, G.J.A. Morphology of the diastereomeric salt of the alkaloid ephedrine and a chlorine substituted cychc phosphoric acid. J. Cryst. Growth 1997, 171, 236-249. 

Phytochemistry All plant parts contain alkaloids. Young shoots have up to 3.5 % alkaloids (ephedrine and pseudoephedrine), tannins, vitamin C, and pigments. The stems contain up to 14 % tannins. The core of the wood stems contained liom 30 % to 65 % tannins. Seeds contained 4 pigments of the flavone series (Khalmatov 1964 Khalmatov et al. 1984). 

Amphetamine is another powerful drug related to the alkaloid ephedrine. Whereas morphine slows down nerve signal transmissions, amphetamine enhances them. Amphetamine is an example of a stimulant, a drug that increases alertness and wakefulness. Amphetamine is widely used to treat Attention-Deficit H)q3eractivity Disorder (ADHD) and is prescribed under the trade name Adderall. Patients suffering from ADHD find that amphetamine helps them to focus and concentrate more effectively. However, because amphetamine produces alertness and increased stamina, it, too, is often abused. 

Crude (mainly raw, cut, and powdered) and extracts extracts normaUy come in 5-9% total alkaloid content. Powdered crude wiaHUANG claimed to contain 6-8% ephedrine has been offered, which should be considered adulterated, as commercial crude twaHUANG normally contains only about 1% ephedrine alkaloids. Ephedrine, ephedrine hydrochloride, and ephedrine sulfate formerly official in U.S.P. 

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