R-(+)-7-羟基-DPAT的药理学特性，一种假定的多巴胺D3受体配体。

Pharmacological aspects of R-(+)-7-OH-DPAT, a putative dopamine D3 receptor ligand.

作者信息

Damsma G, Bottema T, Westerink B H, Tepper P G, Dijkstra D, Pugsley T A, MacKenzie R G, Heffner T G, Wikström H

机构信息

Department of Medicinal Chemistry, University of Groningen, Netherlands.

出版信息

Eur J Pharmacol. 1993 Nov 16;249(3):R9-10. doi: 10.1016/0014-2999(93)90533-n.

DOI:10.1016/0014-2999(93)90533-n

PMID:8287911

Abstract

The R-(+)-isomer of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) bound with a more than 200-fold higher affinity to cloned human dopamine D3 receptors (Ki = 0.57 nM) than to dopamine D2 receptors; the corresponding S-(-)-enantiomer had considerably less affinity for both dopamine receptor subtypes, indicating that the known enantiomer selectivity of 7-OH-DPAT for the 'classical' dopamine D2 receptor subtype extends to the recently discovered dopamine D3 receptor subtype. In rats R-(+)-7-OH-DPAT dose dependently (10-1000 nmol/kg) decreased dopamine release and induced yawning, while sniffing behaviour occurred at the highest dose tested (1000 nmol/kg). The possibility that the inhibition of dopamine release and the elicitation of yawning are mediated by dopamine D3 receptors is considered.

摘要

7-羟基-2-（N，N-二正丙基氨基）四氢萘（7-OH-DPAT）的R-（+）-异构体与克隆的人多巴胺D3受体（Ki = 0.57 nM）结合的亲和力比与多巴胺D2受体高200多倍；相应的S-（-）-对映体对两种多巴胺受体亚型的亲和力都要低得多，这表明7-OH-DPAT对“经典”多巴胺D2受体亚型已知的对映体选择性也延伸至最近发现的多巴胺D3受体亚型。在大鼠中，R-（+）-7-OH-DPAT剂量依赖性地（10 - 1000 nmol/kg）减少多巴胺释放并诱发呵欠，而在测试的最高剂量（1000 nmol/kg）时出现嗅探行为。研究了多巴胺释放的抑制和呵欠的诱发是否由多巴胺D3受体介导的可能性。