Metabolic Activation and Toxicities of bis-Benzylisoquinoline Alkaloids

This chapter introduces the bioactivation and toxicity of bis-benzylisoquinoline alkaloid, particularly their pulmonary toxicity. It starts with a brief description of pharmacological activities of bis-benzylisoquinoline alkaloids, followed by mechanisms of metabolic activation of para-methylene phenol containing compounds and the interactions of reactive metabolites of isoquinoline alkaloids with proteins. A total of four bis-benzylisoquinoline alkaloids, i.e., dauricine, tetrandrine, neferine, and berbamine are discussed as examples. The chapter covers (1) the natural source and pharmacological activities of the bis-benzylisoquinoline alkaloids; (2) identification of reactive metabolites and major cytochromes P450 involved in the metabolic activation of the para-methylene phenol containing compounds; and (3) protein modifications induced by the reactive metabolites of the isoquinoline alkaloids. It also describes a newly developed approach to screen potentially harmful para-methylene phenol containing compounds from complicated mixtures.