ADTN的前体药物：多巴胺能作用的选择性及ADTN的脑内水平

A prodrug of ADTN: selectivity of dopaminergic action and brain levels of ADTN.

作者信息

Horn A S, Kelly P, Westerink B H, Dijkstra D

出版信息

Eur J Pharmacol. 1979 Nov 23;60(1):95-9. doi: 10.1016/0014-2999(79)90056-6.

Abstract

The effects of administration of the prodrug dibenzoyl ADTN (DBADTN) on ADTN concentrations in rat brain and on behaviour in rats having a unilateral 6-hydroxydopamine lesion in the corpus striatum have been studied. Using a combination of HPLC and electrochemical detection as assay method it was found that there was a more selective accumulation of ADTN in the corpus striatum than in the cerebellum. In addition the accumulation of ADTN in the corpus striatum was slow in onset yet long in duration. The peak concentration of ADTN was relatively low and although it was sufficient to cause a strong stimulation of presynaptic DA receptors it did not cause significant rotation in the unilaterally lesioned rat. Prodrug methodology may thus prove useful in designing new selectively acting DA agonists.

摘要

已研究了前药二苯甲酰ADTN（DBADTN）给药对大鼠脑内ADTN浓度以及对单侧纹状体6-羟基多巴胺损伤大鼠行为的影响。采用高效液相色谱法和电化学检测相结合的方法作为测定手段，发现ADTN在纹状体中的蓄积比在小脑中更具选择性。此外，ADTN在纹状体中的蓄积起效缓慢但持续时间长。ADTN的峰值浓度相对较低，虽然足以强烈刺激突触前多巴胺受体，但并未导致单侧损伤大鼠出现明显的旋转行为。因此，前药方法可能在设计新的选择性作用的多巴胺激动剂方面证明是有用的。