Dopamine D1 receptor ligands: where are we now and where are we going.
The dopamine (DA) D(1) receptor is the most highly expressed DA receptor subtype among the DA receptor family. Although the first DA D(1) receptor selective ligand SCH-23390 (1) was introduced more than two decades ago, clinically useful D(1) 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 D(1) receptor. Since then, a number of D(1) 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 D(1) receptor agonists.
Zhang
Jing
J
Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xiong
Bing
B
Zhen
Xuechu
X
Zhang
Ao
A
D000818:Animals; D018491:Dopamine Agonists / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D010617:Phenanthridines / Q000737:chemistry / Q000627:therapeutic use; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000737:chemistry
D018491:Dopamine Agonists; D008024:Ligands; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; C061532:dihydrexidine