N-Sulphoconjugation of alicyclic, alkyl- and aryl-amines in vivo and in vitro

Abstract

Radioactive 35S in 3'-phosphoadenosine 5'-phosphosulphate was incorporated into alicyclic, alkyl- and aryl- amines in the presence of hepatic 105 000 g supernatants of female rats. 4-Phenylpiperazine, 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP), 1,2,3,4-tetrahydroisoquinoline, N-methylbenzylamine, desmethylzotepine and desmethylzimeldine showed the highest conjugation with 35SO3 among the amines tested. Incorporation of 35SO3 into alicyclic and alkyl-amines was higher at pH 10.0 than at pH 7.4 but the incorporation into arylamines was the opposite. A greater amount of 35SO3 was incorporated into the secondary alkylamines than the corresponding primary amines. Radioactive reaction products were identified as N-sulphoconjugates of amines by comparison on t.l.c. with synthetic authentic compounds. Reaction products of desmethylimipramine (DMI) and PTHP in vitro were isolated as their sulphoconjugates, identified by comparison of field desorption mass spectra, u.v. spectra, retention time on h.p.l.c. and RF values on t.l.c. with synthetic standards. DMI N-sulphonate and PTHP N-sulphonate were detected in the body of female rats treated orally with DMI and PTHP, respectively. These results indicate that N-sulphoconjugation is a common metabolic pathway of alicyclic, alkyl- and aryl-amines in vivo and in vitro.

Interindividual variability in the N‐sulphation of desipramine in human liver and platelets.

“…Sulphation of hydroxy groups has been described in human liver and in blood platelets. The hepatic sulphation of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) varies over a range of 5 and 7-fold, respectively, whereas, in platelets, the sulphation of 3-methoxy-4-hydroxyphenylglycol (Anderson et al, 1981) and minoxidil (Johnson & Baker, 1987) varies over a range of 15-fold. Sulphation at nitrogen atoms has received little attention although alkyl-and aryl-amines are N-sulphated in rat liver (Iwasaki et al, 1983(Iwasaki et al, , 1986Johnson et al, 1982;Ramaswamy & Jakoby, 1987). The (Iwasaki et al, 1986).…”

“…The hepatic sulphation of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) varies over a range of 5 and 7-fold, respectively, whereas, in platelets, the sulphation of 3-methoxy-4-hydroxyphenylglycol (Anderson et al, 1981) and minoxidil (Johnson & Baker, 1987) varies over a range of 15-fold. Sulphation at nitrogen atoms has received little attention although alkyl-and aryl-amines are N-sulphated in rat liver (Iwasaki et al, 1983(Iwasaki et al, , 1986Johnson et al, 1982;Ramaswamy & Jakoby, 1987). The (Iwasaki et al, 1986). The plasma concentrations of this drug and its metabolite 4-hydroxy-DMI vary widely among individuals (Hammer & Sjoqvist, 1967) and this variability is believed to reflect variation in the rate of DMI hydroxylation (Sjoqvist & Bertilsson, 1986;Spina et al, 1984Spina et al, , 1987.…”

Selective Role of Sulfotransferase 2A1 (SULT2A1) in theN-Sulfoconjugation of Quinolone Drugs in Humans

“…The present results, in addition to previous reports in rats (Iwasaki et al, 1986), guinea pigs (Ramaswamy and Jakoby, 1987), and rabbits (Yoshinari et al, 1998a;Shiraga et al, 1999b), have demonstrated that a wide variety of amine compounds, including alicyclic amines, alkylamines, and arylamines, serve as substrates for N-sulfation, despite large differences in their overall structures. Both primary and secondary, but not tertiary, amines are subjected to N-sulfoconjugation.…”

“…Conversely, the position sulfated in desipramine constitutes a secondary alkylamine (Fig. 1) (Iwasaki et al, 1986;Ramaswamy and Jakoby, 1987). Therefore, structurally divergent amines act as an acceptor substrate for the N-sulfoconjugation process in animals and in humans.…”

“…Several amine compounds have long been found to be excreted as sulfamates in the urine of mammals (Boyland and Sims, 1959;Iwasaki et al, 1986). Enzymes mediating amine sulfation were isolated from the livers of guinea pigs (Ramaswamy and Jakoby, 1987) and rats (Naritomi et al, 1994).…”