Pseudoephedrine/ephedrine/ephedra

Biotransformation ephedra ephedrine pseudoephedrine tissue culture... 

In the alkaloid synthesis, L-phenylalanine (Figure 30) provides to alkaloid the phenyl or phenylpropyl nucleus. These kinds of nuclei occur in cathionine, cathine, ephedrine, pseudoephedrine and norpseudoephedrine. Such alkaloids are found especially in many species of Ephedra. Natural alkaloid molecules from these plants have similar properties to synthetic compounds used as narcotics (e.g., amphetamine). 

OFFICIAL NAMES Ephedra, Ephedra sinica STREET NAMES Mahuang, ma huang, desert tea, Mormon tea, American ephedra, European ephedra, Pakistani ephedra, ephedrine, ephedrine alkaloids, pseudoephedrine DRUG CLASSIFICATIONS Not scheduled, dietary supplement... 

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. 

Taking ephedra along with other drugs If taken with other drugs simultaneously, ephedra may cause serious complications. Antidepressants, allergy, asthma, or cold medications containing ephedrine, pseudoephedrine or phenylpropanola-... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, amphetamines, bupropion, citalopram, clomipramine, cyproheptadine, desipramine, dextroamphetamine, dextromethorphan, diethylpropion, dopamine, doxepin, entacapone, ephedra, ephedrine, epinephrine, fluoxetine, fluvoxamine, ginseng, imipramine, levodopa, mazindol, meperidine, methamphetamine, nefazodone, nortriptyline, paroxetine, phendimetrazine, phentermine, phenylephrine, pizotifen, propoxyphene, protriptyline, pseudoephedrine, rizatriptan, sertraline, sibutramine, sumatriptan, sympathomimetics, tramadol, tricyclic antidepressants, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Ephedrine and pseudoephedrine have been measured in guinea pig plasma using HPLC with fluorescence detection, following precolumn derivatization with 5-dimethylamino-napthalene-1-sulfonyl chloride in acetonitrile. The mobile phase was 0.6% phosphate buffer (pH 6.5)-methanol (3 8 v/v). Jacob et al. developed an LC-atmospheric pressure chemical ionization MS-MS method for the quantitaion of various alkaloids found in ephedra-containing dietary supplements and also in plasma and urine from subjects using these supplements. Using this method, the concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine and caffeine were determined in low nanogram quantities in plasma and urine. The analytical cycle time for this method was 12 min. 

All ephedra plants contain phenylalanine-derived alkaloids. These include (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)-norpseudo-ephedrine (also called cathine because it is a major alkaloid of Catha edulis or khat, a plant used as a stimulant in North Africa), (-)-A-methylephedrine and (+)-A-methylpseudoephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine). Significant enantioselective differences with regard to both pharmacokinetic and pharmacodynamic effects of these agents are possible. All of these alkaloids have important effects on the cardiovascular and respiratory systems, but not to the same degree. 

Known as ma huang in Chinese medicine, this is a large genus of woody, jointed, desert shrubs. These shrubs appear to be leafless from a distance, but on close inspection possess scale-like leaf structures at the nodes. Ephedrine, pseudoephedrine, and related alkaloids are the active principles. Ephedra is marketed for many logical purposes, e.g. as decon-... 

Ephedrine, (+)-pseudoephedrine, (—)-A-methylephedrine Ephedra sinica and phytopreparations 20 mM Tris-phosphate (pH 2.5), 20 mg/mL DM-PCD, 5 % tetrabutylammonium chloride UVat210nm [57]... 

Ephedrine, (+)-pseudoephedrine Ephedra herb phytopreparations NACE 80 mM ammonium acetate, 3 % acetic acid in methanol LIF ex 488, em 520 [64]... 

Phinney et al. developed three CE-UV methods that allowed the enantiose-paration of ephedrine and pseudoephedrine using neutral HP-pCD, DM-pCD, and charged sulfated pCD as chiral selectors. The combination of negatively charged sulfated pCD (2.8 %) and DM-pCD (1.2 %) under acidic conditions (pH 2.5) provided the best separation of the two couples of enantiomers. Standard reference materials (SRMs) containing ephedra in development at NIST were analyzed by each of three CE methods. In the SRM samples, only the naturally occurring enantiomers ( )-ephedrine and (-l-)-pseudoephedrine were found however, the method proved to be suitable in detecting product adulteration by its potential in identification of specific stereoisomers [56]. The neutral HP-pCD was also found to be a useful chiral selector in the presence of tetrabutylammonium chloride as additive, for the simultaneous enantioseparation of ephedrine, pseudoephedrine, iV-methylephedrine, and norephedrine enantiomers in Ephedra sinica extracts [57]. 

Ephedras contain various alkaloids, primarily (-)-ephedrine, (+)-pseudoephedrine and the corresponding nor and N,N-dimethyl derivatives. Ephedrine is structurally similar to adrenaline and physiologically is an indirect sympathomimetic. Dietary supplements containing ephedras are widely used in weight reduction and energy enhancement (100). 

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. 

N.A. Ephedra nevadensis Wats. Pseudoephedrine, 1-ephedrine, d-pseudoephedrine.100 A decongestant and asthma remedy, for hypertension, hay fever. 

The thought that transmethylation of noradrenaline may be an initial step in its deactivation in the body makes one wonder whether further transmethylation of adrenaline is also not a common biological process. As a result of studies of the various alkaloids of plants of the Ephedra species, it was noted that not only Z-ephedrine and its stereoisomer d-pseudoephedrine are present but also that -norephedrine, d-norpseudoephedrine, l-methylephedrine, and d-methylpseudoephedrine (8) are present. The quaternary tri-methylammonium compounds corresponding to these were not reported but very... 

Various species of Ephedra grow in different parts of the world. It is believed that the Chinese species contain the official levorotatory ephedrine, whereas the same species and other varieties from Europe yield only dextrorotatory pseudoephedrine. East Indian species range from rich to none. Ephedrine exists in the seed of another, totally unrelated Indian plant, Sida cordifolia, which was also used in folk medicine. Ma huang also contains another alkaloid, ephedine, which lowers blood pressure and has other complex actions. 

Since clandestine lab operators use ephedra to make methamphetamine, the DEA monitors supplements containing ephedrine. One kilogram of ephedrine, the equivalent of 48,000 25-mg ephedrine tablets, can be used to produce anywhere from 1.1 to 1.6 lbs (.5 to 0.75 kg) of methamphetamine in a drug lab. Pseudoephedrine can be used for the same purpose. 

Ephedrine is a component of the traditional Chinese remedy Ma Huang, extracted from Ephedra species, it is also used in nasal sprays as a decongestant. Pseudoephedrine is the active component of the decongestant Sudafed (so should that be Pseudephed ). 

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