Methylephedrine elimination

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. 

Synthesis of the acyclic portion began, as in the previous synthesis, with enantiomerically pure citronellol (25). Protection of the alcohol as the benzyl ether and oxidative cleavage of the olefin to the aldehyde gave 26 (85%). Chain extension via the masked acyl anion equivalent 27, alcohol protection, and concomitant -elimination and isomerization of the allene to die alkyne with butyl lithium gave 28. The resulting protected ketone must now be converted to the P-alcohol required for the completion of the synthesis. Thus hydrolysis to die ketone followed by enantioselective reduction with (—)-N-methylephedrine-... 

The early literature describes examples of elimination reactions of a rather forcing nature which have not been explored further. For example, the elimination of HCl from (2-chloroethyl)phosphonic dichloride occurs over BaCl2 at 330 and dechlorination of (l,2-dichloroethyl)phosphonic diesters occurs on heating with zinc dust. Dehydrochlorination of a (2-chloroalkyl)phosphonic acid occurs on simple pyrolysis but the preferred procedure consists in the treatment of the acid diester with Et3N in warm benzene, a procedure also used for analogous (2-chloroethyl)phosphinic esters ". The dehydro-halogenation of isopropyl (2-haloethyl)phenylphosphinate by a chiral tertiary amine, such as quinine, quinidine, 1 -phenylethylamine or A-methylephedrine, in a less than equivalent quantity, affords an enrichment of one enantiomer of the ethenylphenylphosphinic... 

The interaction of a (2-halogenoethyl)phosphinate (129) with less than one molar proportion of a chiral base [(—)-quinine, (+)-quinidine, (+)-l-phenyl-ethylamine, and (—)-A -methylephedrine, were each used] results in elimination to give (130) with concurrent enrichment of the less reactive phosphinate enantiomer (129). The leaving group evidently plays a significant role in the... 

The biotransformation of ephedrine proceeds via demethylation to norephedrine and via oxidative deamination followed by conjugation, in analogy to the metabolism of amphetamine. Over 90% is eliminated via the kidneys within 24 h, up to 75% unchanged, 8-20% as norephedrine and the rest after oxidative deamination. Methylephedrine is 33% unchanged and is 8% excreted as ephedrine. The excretion rate also depends on the pH of the urine. Desmethylpropylhexedrine and 4-hydroxypropylhexedrine, metabolites of propylhexedrine, can be determined in the urine [44]. Prolintane, a benzylbutylpyrrolidine product, is to some extent changed oxidatively in the liver. This mainly produces hydroxylated metabolites, but also produces... 

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See also in sourсe #XX -- [ ]

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