Metabolic Fate of Methoxamine and N-Isopropylmethoxamine

Intra-anal and rectal application of l-erythro methoxamine gel increases anal resting pressure in healthy volunteers

“…Intra‐anal application may result in a better MARP response, as the absorptive surface area may be improved by the anal columns and the diffusion distance to the IAS is shorter. In the dog, methoxamine undergoes dealkylation to 2‐hydroxymethoxamine28. Metabolic dealkylation of L ‐erythro methoxamine via the hepatocyte cytochrome P450 mono‐oxygenase system may occur to a greater degree following rectal application, because of an increased first‐pass effect.…”

Application of chemical ionization mass spectrometry to the study of stereoselective in vitro metabolism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane

“…Based on inspection, amine 1 may be metabolized according to several possible pathways as shown in Scheme I. Oxidation of the aromatic methyl group to the and carboxyl functions has been shown byHo and Tansey (16) to give rise to the major urinary metabolites in rat. By analogy with other 1-phenyl-2-aminopropanes additional pathways may be expected to proceed through oxidative deamination ( 1 7 ) to give 3 and 5 , hydroxylation(18) and further side chain oxidation to the benzoic acid ( 1 9 ) , and finally 0-demethylation of the aromatic methoxy groups to give 7a and 7b(20). There are thus five feasible sites of metabolism, each having a differ-ANALYTICAL CHEMISTRY, VOL.…”

Chemical conversion of the psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane to 5-hydroxy-2,6-dimethylindole

“…The possibility that the p-quinone 2 may also undergo intermolecular covalent bond formation with nucleophilic moieties of macromolecules has been offered as an explanation for the ability of this molecule to destroy noradrenergic terminals.8 Consistent with this proposal, tritium-labeled 1 has been shown to form irreversible bonds with proteins.9 The polarity of 6hydroxydopamine precludes its passage across the blood brain barrier, although irreversible depletion of brain norepinephrine stores has been reported for centrally administered 6-hydroxydopamine. 10 Our interest11 in the metabolism and mechanism of action of the psychotomimetic compound l-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (4), commonly referred to as "DOM," and the structural analogy between 6-hydroxydopamine and the bis-O-demethylated compound 5, a potential metabolite of amine 4 (for examples of oxidative O-demethylations, see ref 12), has prompted us to prepare the p-hydroquinone 5 as an aid to its identification in the urine of animals treated with 4 and in tissue homogenates Aqueous hydrobromic acid treatment of amine 4 followed by attempted isolation of the aminophenol 5 at pH 9.5 provided a compound in good yield which proved to be not the desired product 5 but rather 5-hydroxy-2,6-dimethylindole (7). Chemical ionization mass spectral (cims)13 analysis gave a molecular ion (MH+) at 162 corresponding to protonated 7.…”