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

Abstract

1. Radioactive ³⁵S in 3′-phosphoadenosine 5′-phosphosulphate was incorporated into alicyclic, alkyl- and aryl-amines in the presence of hepatic 105 000g supernatants of female rats. 4-Phenylpiperazine, 4-pheny1-1,2,3,6-tetrahydropyridine (PTHP), 1,2,3,4-tetrahydroisoqumoline, N-methylbenzylamine, desmethylzotepine and desmethylzimeldine showed the highest conjugation with ³⁵SO₃ among the amines tested.

2. 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.

3. Radioactive reaction products were identified as N-sulphoconjugates of amines by comparison on t.l.e. 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 R_F values on t.l.c. with synthetic standards.

4. DMI N-sulphonate and PTHP N-sulphonate were detected in the body of female rats treated orally with DMI and PTHP, respectively.

5. These results indicate that N-sulphoconjugation is a common metabolic pathway of alicyclic, alkyl- and aryl-amines in vivo and in vitro.