PRAMIPEXOLE BINDING AND ACTIVATION OF CLONED AND EXPRESSED DOPAMINE D-2, D-3 AND D-4 RECEPTORS

被引：230

作者：

MIERAU, J

SCHNEIDER, FJ

ENSINGER, HA

CHIO, CL

LAJINESS, ME

HUFF, RM

机构：

[1] BOEHRINGER INGELHEIM KG,DEPT BIOCHEM RES,W-6507 INGELHEIM,GERMANY

[2] UPJOHN CO,CELL BIOL,KALAMAZOO,MI 49001

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1995年 / 290卷 / 01期

关键词：

DOPAMINE RECEPTOR SUBTYPE; PRAMIPEXOLE (SND 919);

D O I：

10.1016/0922-4106(95)90013-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propylamino-benzthiazole-dihydrochloride) is a potent dopamine autoreceptor agonist. We have carried out an analysis of the binding affinities of dopamine D-2L, D-2S, D-3, and D-4 receptors for pramipexole using both [H-3]pramipexole and [H-3]spiperone as radioligands at cloned and heterologously expressed receptors. Studies were carried out using rat and human D-2L, D-2S and D-3 receptors with equivalent results. When the binding of pramipexole to the high affinity, guanine nucleotide-sensitive state of each receptor was analyzed, pramipexole is most selective for D-3 compared to D-2 and D-4 receptors. These results indicate a 5-fold selectivity of pramipexole for D-3 receptors, while quinpirole and bromocriptine are non-selective or more D-2/D-4 receptor selective. Two measurements of receptor activation for dopamine D-2, D-3, and D-4 receptors also show that pramipexole is most potent for activation of D-3 receptors. The dopamine D-3 receptor selectivity of pramipexole may explain the previously described properties of this drug, including its potent autoreceptor preference.

引用

页码：29 / 36

页数：8

共 23 条

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