Dopamine D1 receptor ligands: Where are we now and where are we going

  1. Jing Zhang1,
  2. Bing Xiong2,
  3. Xuechu Zhen3,*,
  4. Ao Zhang1,*

Article first published online: 18 JUL 2008

DOI: 10.1002/med.20130

Issue

Medicinal Research Reviews

Medicinal Research Reviews

Volume 29, Issue 2, pages 272–294, March 2009

Additional Information

How to Cite

Zhang, J., Xiong, B., Zhen, X. and Zhang, A. (2009), Dopamine D1 receptor ligands: Where are we now and where are we going. Med. Res. Rev., 29: 272–294. doi: 10.1002/med.20130

Author Information

  1. 1

    Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

  2. 2

    Discovery Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

  3. 3

    Neuropharmacological Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

*Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Publication History

  1. Issue published online: 27 JAN 2009
  2. Article first published online: 18 JUL 2008

Funded by

  • Chinese National Science Foundation. Grant Number: 30672517
  • Shanghai Commission of Science and Technology. Grant Number: 07pj14104
  • Ministry of Science and Technology. Grant Number: 2007AA02z163

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Keywords:

  • dopamine;
  • dopamine receptor;
  • benzazepine;
  • dihydrexidine;
  • Parkinson's disease

Abstract

The dopamine (DA) D1 receptor is the most highly expressed DA receptor subtype among the DA receptor family. Although the first DA D1 receptor selective ligand SCH-23390 (1) was introduced more than two decades ago, clinically useful D1 receptor selective ligands are rare. A renewed interest was ignited in the early 1990s by Nichols and Mailman who developed dihydrexidine (27a), the first high affinity full efficacy agonist for the D1 receptor. Since then, a number of D1 receptor agonists with full intrinsic activity, including A-86929 (31a), dinapsoline (32a), dinoxyline (34a), and doxanthrine (35a) were identified. These compounds all contain a conformationally rigid structure. However, the fate of such ligands for clinical use as treatments of Parkinson's disease and other related CNS disorders is not optimistic since the clinical trial with dihydrexidine (27a) was not successful. Further investigations on other compounds which are currently in the discovery stage will be crucial for determining the future of the D1 receptor agonists. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 2, 272–294, 2009

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