Confirming urinary excretion of mephentermine and phentermine following the ingestion of oxethazaine by gas chromatography-mass spectrometry analysis.

Mephentermine and phentermine, substances prohibited in sports by the World Anti-Doping Agency, were found for the first time in urine specimens following the administration of a therapeutic medication, oxethazaine. In a recent sporting event, a urine specimen donor who tested positive for mephentermine and phentermine claimed consumption of Mucaine((R)) for treating stomach pain was the reason for testing positive. Five volunteers were administrated oxethazaine (a topical anesthetic found in the multi-ingredient medication Mucaine and its generic equivalent, Stoin, both of which are available in Taiwan), mephentermine, and phentermine. Excretion profiles of mephentermine and phentermine following the administration of these drugs were found to be similar. However, the mephentermine/phentermine ratios found in urine specimens collected at different time points following the administration of oxethazine and mephentermine were found to be characteristically different.

Oxethazaine as the source of mephentermine and phentermine in athlete's urine.

The urine specimens of numerous athletes were found to be positive for mephentermine both in-competition and out-of-competition in Taiwan. The donor of one specimen claimed she had only taken Mucaine (contains oxethazaine) for relieving symptomatic peptic ulcer and gastritis. Oxethazaine is not included in the prohibited list of the World Anti-Doping Agency; however, its metabolized compounds, mephentermine and phentermine, are included in that list. This study applied LC-MS-MS to analyze the excretions of three volunteers who ingested oxethazaine and presented positive results for mephentermine and/or phentermine. Thus, oxethazaine is the source of mephentermine and phentermine. Moreover, the results showed that 48 brands of gastric medicines containing oxethazaine were legally imported or locally manufactured in Taiwan, information which could be useful for limiting the misuse of oxethazaine by athletes. The data suggested that the sports associations should warn athletes about the risks of taking oxethazaine.

Mephentermine hemisulfate monohydrate: an adrenergic agent.

The title molecule, a hydrated hemisulfate salt of ethyl(2-methyl-1-phenyl-2-propyl)ammonium, C11H18N+.0.5SO4(2-).H2O, consists of a phenethylamine skeleton in which the N atom is protonated. There are two molecules in the asymmetric unit, with the S atom of the SO4(2-) ion lying on a pseudo-twofold axis. The ethylamine side chain is in an extended conformation in both the symmetry-independent molecules. The distance of the N atom from the centre of the benzene ring is 5.1 A for molecule 1 and 5.3 A for molecule 2. The packing is stabilized by N-H...O and O-H...O hydrogen bonds.

Metabolism of mephentermine and its derivatives by the microsomal fraction from male Wistar rat livers.

1. The N-demethylation of mephentermine (MP), p-hydroxymephentermine (p-hydroxy-MP) and N-hydroxymephentermine (N-hydroxy-MP), to produce phentermine (Ph), p-hydroxyphentermine (p-hydroxy-Ph) and N-hydroxyphentermine (N-hydroxy-Ph), and the p-hydroxylation of MP and Ph, to produce p-hydroxy-MP and p-hydroxy-Ph, were examined using rat liver microsomal preparations containing NADPH. Microsomal reduction of N-hydroxy-Ph to Ph was also examined using various cofactors. In addition, enzymic system for the N-demethylation and p-hydroxylation were examined using various inhibitors. 2. N-Hydroxy-MP demethylation to N-hydroxy-Ph proceeded at a rate almost 10-fold faster than other reactions. MP demethylation to Ph, MP oxidation to P-hydroxy-MP, Ph oxidation to p-hydroxy-Ph proceeded at similar rates, whilst p-hydroxy-MP demethylation to p-hydroxy-Ph was catalysed at the slowest rate. Microsomal reduction of N-hydroxy-Ph to Ph required NADH, and the activity was similar to that of MP oxidation to p-hydroxy-MP. 3. N-Demethylation of MP, p-hydroxy-MP and N-hydroxy-MP were inhibited not only by inhibitors of cytochrome P450, but also by methimazole, an inhibitor of the FAD-monooxygenase system. p-Hydroxylations of MP and Ph were inhibited only by inhibitors of cytochrome P450.