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 desmethylzimelidine showed the highest conjugation with 35SO3 among the amines tested. Incorporation of 35SO3 into alicyclic and akly-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 second alkylamines than the corresponding primary amines. Readioactive 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.