Fungal transformations of antihistamines: metabolism of methapyrilene, thenyldiamine and tripelennamine to N-oxide and N-demethylated derivatives

Abstract

1. Strains of the fungus Cunninghamella elegans ATCC 9245 and 36112 were tested for their ability to transform the antihistamines methapyrilene (I), thenyldiamine (II) and tripelennamine (III). 2. Antihistamine metabolites were isolated by h.p.l.c., and identified by their 1H-n.m.r. and mass spectral properties. 3. All three drugs were transformed by both C. elegans strains to N-oxidized and N-demethylated derivatives. Metabolism during 96 h of incubation amounted to 85% for (I), 64% for (II), and 83% for (III). Metabolites soluble in organic solvents amounted to 62% to 86% of the total metabolism; approximately 88% to 95% of the organic-soluble metabolites were N-oxide derivatives of each antihistamine.