Amphetamine 4-hydroxy

NB See Amphetamine and Amphetamine, 4-hydroxy, for further details. Alternative calculation medtod gave pJC i = 9.49 and = 10.78. 

Warren RJ, Begosh PP and Zarembo JE, Identification of amphetamines and related sympattiomimetic amines, /. Assoc. Off. Anal. Chem., 54,1179-1191 (1971). NB See Amphetamine and Amphetamine, 4-hydroxy, for furdter details. Lewis (see no. 1094, Phenylpropanolamine) reported pKai = 9.59 and = 9.71. 

RESPONSE I did not show that the N-hydroxy analog of MDA is not MDMA-like. I showed that it is not amphetamine-like. 

COMMENT/QUESTION I was not using MDMA-like in the sense that you were using it—as a substitute. I am simply saying it did not have the pharmacologic effect that MDMA had namely, substitution for amphetamine, which obviously must mean that the N-hydroxy compound is not converted to MDMA to the same extent at least as the p-toluylamphetamine analog was. I would like to know if you have any information about the metabolism of those N-hydroxy compounds. 

RESPONSE We have not looked at that at all. But it is surprising. 1 expected to see either hydroxylation or dehydroxylation, so 1 expected to see similar activities. But this is what we see. If you compare the activities on a milligram per kilogram basis, the N-hydroxy amphetamine appears to be equipotent. However, when you look at the molecular weights (it is a different salt), it is in fact twice as potent. 1 cannot explain that. 

Deminiere, J.M. Simon, H. Herman, J.P. and Le Moal, M. 6-Hydroxy-dopamine lesion of the dopamine mesocorticolimbic cell bodies increases (-l-)-amphetamine self-administration. Psychopharmacology 83 281-284, 1984. 

As it can be observed in Fig. 2, three out of the 16 investigated compounds, namely, heroin, lysergic acid diethylamide (LSD), and its metabolite 2-oxo, 3-hydroxy-LSD (O-H-LSD), were not detected in any wastewater sample. Two other target analytes, 6-acetyl morphine (6ACM) and A9-tetrahydrocannabinol (THC), were only present in influent wastewaters and with low detection frequencies. The most ubiquitous compounds, present in all influent and effluent wastewater samples analyzed, were the cocaine metabolite benzoylecgonine, and the amphetamine-like compounds ephedrine (EPH) and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Cocaine, cocaethylene (CE, transesterification product of cocaine formed after the joint consumption of cocaine and ethanol), and morphine (MOR) were detected in all influent, but not in all effluent wastewaters (see Fig. 2). 

Agilent ChemStation software, 29-31, 33 Alkylquinaxolines, in Phodopus roborovskii, 19 Allomones, 13 2-Aminoacetophenon, 155 2-Amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid, see Felinine Amniotic fluid, odour of, 194 Amphetamine, 266... 

Amphetamine is metabolized by deamination, oxidation, and hydroxylation. Figure 4.1 illustrates the metabolic scheme for amphetamine. Deamination produces an inactive metabolite, phe-nylacetone, which is further oxidized to benzoic acid and then excreted in urine as hippuric acid and glucuronide conjugates. In addition, amphetamine is also converted to norephedrine by oxidation and then this metabolite and the parent compound are / -hydroxylated. Several metabolites, including norephedrine, its hydroxy metabolite, and hydroxy amphetamine, are pharmacologically active. The excretion of amphetamine depends on urinary pH. In healthy men who were administered 5 mg of isotopically labeled d,l-amphetamine, approximately 90% of the dose was excreted... 

NaOH, and extracted with 4x100 mL CH2C12. Removal of the solvent under vacuum yielded 3.5 g of a viscous off-white oil that was distilled at 160 °C at 1.3 mm/Hg to give 2.0 g of a white viscous oil. The pot residue remained fluid, but was discarded. This distillate was dissolved in 8.0 mLIPA to give, eventually, a clear solution. This was neutralized with concentrated HC1 and diluted with 100 mL anhydrous EtjO. The loose white crystals of 3,4-methylenedioxy-N- (2-hydroxy-ethyl)amphetamine hydrochloride (MDHOET) that formed were removed by filtration, washed with Etp, and air dried. These weighed 2.3 g, and had a mp of 147-148 °C. Anal. (C 2H,8C1N0,) N. 

The presence of a potentially active impurity in TMA deserves some comment. In the Canadian work, the material used was described as melting at 219-220 °C, which is the property given for the impurity-free material above. If this was the actual material used in those studies, this impurity (3,5-dimethoxy-4-hydroxy-amphetamine) was probably not present. The Army studies use a material of unreported melting point. In my own studies, the lower melting product was used. 

The main metabolic reaction is the deamination of amphetamine with the formation of phenylacetone, which is subsequently oxidized to benzoic acid, then conjugated with glycine to form hippuric acid. Side reactions include aromatic hydroxylation to form 4-hydroxyamphetamine (an active metabolite), the stereoselective [i-hydroxy-lation for the isomer (+) of amphetamine leading to the formation of norephedrine (phenylpropanolamine) and finally the N-oxidation leading to the formation of a hydroxylamine derivative. The products of the hydroxyl and aromatic N-oxides can be conjugated with sulfate or glucuronic acid [18]. 

Quinidine Gluconate Pseudoephedrine Hydro- 189-192 Hydroxy amphetamine Hydro-... 

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