METABOLITES FROM TERTIARY AMINES--PHENCYCLIDINE

建议进行调查以评估其生物医学意义。 细胞色素P-450介导的金属离子代谢形成的中间产物 叔胺。苯环利定将作为模型化合物用于检测 这些亲电离子对生物大分子的反应性。 代谢依赖性抑制的生化机制 苯环利定的细胞色素P-450酶活性将被研究 利用肝微粒体制剂进行体外重组、纯化 细胞色素P-450系统。亚胺物种将被合成，他们的 将研究模型化合物的反应性，并研究其结构 形成的加合物将用质谱学方法进行表征。广度 亚胺中间体的形成是组织和组织特有的 物种将通过14CN-捕集方法确定。 关于金属亚胺中间体的形成及其反应的文献 生物大分子应该提供对分子机制的洞察 与叔胺的有毒行为有关，其中许多是 有用的治疗剂。

Investigations are proposed to assess the biomedical significance of iminium intermediates formed via cytochrome P-450 mediated metabolism of tertiary amines. Phencyclidine will be used as a model compound to examine the reactivity of these electrophilic ions towards biomacromolecules. Biochemical mechanisms underlying metabolism-dependent inhibition of cytochrome P-450 enzymic activities by phencyclidine will be investigated using hepatic microsomal preparations in vitro and reconstituted, purified cytochrome P-450 systems. Iminium species will be synthesized, their reactivity towards model compounds will be studied, and the structure of adducts formed will be characterized by mass spectral methods. The extent to which the formation of iminium intermediates is specific to tissues and species will be determined by use of 14CN- trappping methods. Documentation of the formation of iminium intermediates and their reactions with biomacromolecules should provide insight into the molecular mechanisms associated with the toxic actions of tertiary amines, many of which are useful therapeutic agents.