A H Beckett’s research while affiliated with University of London and other places

... The mass spectra of the condensation products exhibited base ions at m/z 57 (norephedrine) or 71 (ephedrine), and were consistent with formation of the corresponding oxazolidines as depicted in Fig. 2A. Both norephedrine [23] and ephedrine [24,25] are known to form oxazolidines upon reaction with formaldehyde. The net change in molecular weight for the oxazolidines relative to the unreacted amines is an increase of 12 units (M + 12), corresponding to the addition of the methylene group across the oxygen and amine moieties. ...

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Partial conversion of methanol to formaldehyde in the gas chromatography injection port and reactivity with amines

... Oral Administration. The first report of (−)-MAMP pharmacology in humans was published in 1973 by Beckett et al. 23 In this work, the urinary pharmacokinetics of unchanged and metabolized (+)-MAMP and (−)-MAMP were considered alongside those of ethyl-, n-propyl-, and n-butyl-amphetamine. After oral administration of the study drug (12.45 mg of methamphetamine HCl), urine specimens were collected from participants (N = 6) every half hour for the first 4 h, hourly up to 12 h, with intervals increasing in duration up to 24 and 48 h. ...

Reference:

Pharmacology of R -(−)-Methamphetamine in Humans: A Systematic Review of the Literature

... All reagents and solvents (HPLC grade) were commercial products of the highest available purity, and were used as supplied. (±)-N-methyl-α-methyl-dopamine hydrobromide was synthesized in four steps, from commercially available 3,4-dimethoxy-benzaldehyde and nitroethane, through procedures previously reported [32][33][34][35]. 5-(Glutathion-S-yl)-N-methyl-α-methyldopamine 1 and 5-(Nacetylcystein-S-yl)-N-methyl-α-methyldopamine 2 were synthesized through our recently reported one-pot electrochemical procedure [31]. ...

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Environmentally Friendly Expeditious One-Pot Electrochemical Synthesis of Bis-Catechol-Thioether Metabolites of Ecstasy: in vitro Neurotoxic Effects in the Rat Hippocampus

... The metabolism of nitrogen-containing functional groups has become a topic of considerable interest since the early discovery that N-hydroxylated intermediates are often responsible for the toxic and/or carcinogenic properties of aromatic amines, hydrazines, and amides (1). On the other hand, the more facile N-oxygenation of secondary and tertiary alkylamines to hydroxylamines and N-oxides was considered as a route for detoxication (2,3), and it was generally assumed that the strongly basic nitrogen compounds were metabolically stable. However, we have demonstrated that even the protonated hydrophilic amidines (4 -6), as well as diamidines such as pentamidine and diminazene and also guanidines and amidinohydrazones, are capable of undergoing metabolic N-oxygenation by liver microsomal cytochrome P450 monooxygenases (7,8). ...

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Isolation and Characterization of the Protein Components of the Liver Microsomal O2-insensitive NADH-Benzamidoxime Reductase

... 147 When nicotine N-oxide was orally administered to humans or rats, significant amounts of nicotine were excreted in the urine. 31,148 This was not observed after intravenous administration, 148 suggesting that the conversion of nicotine N-oxide to nicotine is mediated by intestinal tissues and/or gut contents. Indeed, rat intestine homogenates, as well as gut contents, were shown to catalyze nicotine N-oxide reduction under anaerobic conditions. ...

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Gut microbiota in reductive drug metabolism

... 1.6 mg/g. The resulting dosage per recommended serving matches roughly earlier reports concerning IPNS-containing tablets from 2014,6 where ca.20-40 mg per serving (tablet) was found in the context of follow-up investigations into serious adverse events. Urine samples collected after the ingestion of ca. ...

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Mass spectrometric identification and characterization of urinary metabolites of isopropylnorsynephrine for doping control purposes

... Indeed, rat intestine homogenates, as well as gut contents, were shown to catalyze nicotine N-oxide reduction under anaerobic conditions. 149 However, the oral administration of nicotine N-oxide to germ-free or antibiotics-treated rats led to urinary nicotine excretion to the extents similar to those in conventional or non-antibiotic-treated rats. 149 These results indicate that nicotine N-oxide reduction is mediated mainly by host enzymes and/or nonenzymatic processes, with a minimal contribution by the gut microbiota. ...

Reference:

Gut microbiota in reductive drug metabolism

... In the first step, racemic 1-(10H-phenothiazin-10-yl)propan-2ol (±)-3 was synthesized according to the method described by Clement et al. [59], in which propylene oxide (2) was regiose-lectively opened by phenothiazine (1) in the presence of n-butyllithium (n-BuLi) at ambient temperature providing desired alcohol (±)-3 in 64-77% yield depending on the applied scale and the purification method (see Supporting Information File 1). Paradoxically, the product was obtained in higher yield when the reaction was performed on a bigger scale, and when the product was isolated by vacuum distillation instead of column chromatography (SiO 2 ). ...

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First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

... Nonetheless, the urine sample of the athlete who ingested Mucaine 1 did not have phentermine as one of the metabolites, which was inconsistent with the pharmaceutical manufacturer's information [12]. Beckett and Bé langer reported that mephentermine can be metabolized in vivo by oxidative dealkylation to yield phentermine as its major metabolite [13]. The NOC searched unsuccessfully for an explanation for these extraordinary test phenomena of tests. ...

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

... Mammalian metabolism of N-alkylamphetamines is species dependent, and products formed in in vivo studies differ from those formed in vitro (8)(9)(10)(11). The supernatant fraction of rat liver homogenate converted NPA to six products (9), which were the results of C-oxidation (IIa, IIb, and IIIa) and N-oxidation (IVa, IVb, and V), but no p-hydroxylated products (Ib) were formed. In contrast, in vivo metabolism of NPA in rats (10) resulted in C-oxidation (Ib, IIb, and IIIa) but not N-oxidation. ...

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Metabolism of (±)-N-(n-propyl)amphetamine by Cunninghamella echinulata