Forrest I S, Green D E, Serra M T, Soave O A
Psychopharmacol Commun. 1975;1(1):51-9.
The use of tritiated chlorpromazine to correlate total excretion of radioactivity with characterization of the radioactive metabolites had shown a substantial discrepancy. While radioactivity was totally excreted and accounted for within three weeks, recognizable chlorpromazine metabolites represented only about two thirds of the radioactivity in any given sample. To rule out tritium exchange, 14C-labeled chlorpromazine was administered to Rhesus monkeys. The same discrepancy was observed, primarily in the conjugated drug fraction. Therefore, all unconjugated chlorpromazine metabolites were exhaustively extracted, and an alkaline hydrolysis performed. The aglycones liberated thereby were again carefully removed, and the residual aqueous fraction was subjected to an acid hydrolysis. This procedure yielded an additional group of known and unknown phenolic chlorpromazine aglycones, representing approximately one third of the radioactivity in the whole urine. Preliminary trials on urine pools of patients chronically dosed with chlorpromazine yielded essentially the same results. The structure of this new class of chlorpromazine conjugates has not yet been elucidated, nor is the ligand known at this time. A glucoside-type bond may characterize this significant class of chlorpromazine.
使用氚标记的氯丙嗪来关联放射性总排泄量与放射性代谢物的特征，结果显示出显著差异。虽然放射性在三周内完全排泄且得到了 accounted for（此处原文可能有误，推测是 accounted），但在任何给定样本中，可识别的氯丙嗪代谢物仅占放射性的约三分之二。为排除氚交换，给恒河猴施用了14C标记的氯丙嗪。观察到了相同的差异，主要存在于结合药物部分。因此，对所有未结合的氯丙嗪代谢物进行了彻底提取，并进行了碱性水解。由此释放出的苷元再次被仔细去除，剩余的水相部分进行了酸性水解。该程序产生了另外一组已知和未知的酚类氯丙嗪苷元，约占全尿中放射性的三分之一。对长期服用氯丙嗪的患者尿液池进行的初步试验得出了基本相同的结果。这类新的氯丙嗪结合物的结构尚未阐明，目前其配体也未知。一种糖苷型键可能是这类重要的氯丙嗪的特征。
