芳基叠氮帕罗西汀的合成与表征。一种新型的5-羟色胺转运体光亲和探针。

Synthesis and characterization of an aryl-azidoparoxetine. A novel photo-affinity probe for serotonin-transporter.

作者信息

Chudzik J, McCarthy D, Bakish D, Ravindran A, Hrdina P D

机构信息

Department of Psychiatry, University of Ottawa, Ontario, Canada.

出版信息

Biochem Pharmacol. 1995 Oct 12;50(8):1211-5. doi: 10.1016/0006-2952(95)00260-7.

DOI:10.1016/0006-2952(95)00260-7

PMID:7488236

Abstract

Paroxetine is an effective antidepressant drug and potent serotonin (5-HT) uptake inhibitor. It selectively labels 5-HT transporter on platelets and neurons. We report here the synthesis of an aryl-azido derivative of paroxetine, which is a novel photoactive and irreversible ligand for the [3H]paroxetine binding site on the platelet 5-HT transporter. The compound inhibited [3H]paroxetine binding (IC50, 55 nM) and 5-HT uptake (IC50, 12 nM) at equilibrium conditions and inactivated 10-20% of [3H]paroxetine binding sites upon irradiation at 320 nm. SDS-PAGE of platelet protein extract labelled with the radioactive analogue of the synthesized probe revealed the presence of four radioactive bands of which the 71-kDa one was the most prominent.

摘要

帕罗西汀是一种有效的抗抑郁药物，也是一种强效的血清素（5-羟色胺，5-HT）摄取抑制剂。它能选择性地标记血小板和神经元上的5-HT转运体。我们在此报告帕罗西汀芳基叠氮衍生物的合成，该衍生物是血小板5-HT转运体上[3H]帕罗西汀结合位点的一种新型光活性不可逆配体。该化合物在平衡条件下抑制[3H]帕罗西汀结合（IC50，55 nM）和5-HT摄取（IC50，12 nM），并在320 nm照射后使10%-20%的[3H]帕罗西汀结合位点失活。用合成探针的放射性类似物标记的血小板蛋白提取物的SDS-PAGE显示有四条放射性条带，其中71 kDa的条带最为明显。