New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease

• Published in: Frontiers in biology Vol. 10; no. 3; pp. 230 - 238
• Main Authors: Kim, Young-Cho, Alberico, Stephanie L, Emmons, Eric, Narayanan, Nandakumar S
• Format: Journal Article
• Language: English
• Published: Beijing Higher Education Press 01-06-2015
• Subjects: adverse effects; agonists; behavior disorders; binding capacity; bioavailability; Biochemistry; Biomedical and Life Sciences; Cell Biology; cerebral cortex; cognition; Developmental Biology; dopamine; dopamine receptors; drugs; Genetics and Population Dynamics; Life Sciences; Neurobiology; Parkinson disease; Proteomics; Review; second messengers; 信号通路; 多巴胺受体; 帕金森氏病; 治疗; 生物利用度; 神经递质; 精神病; 靶向药物; D1DR; cognition; dyskinesia; dopamine D1 receptor
• ISSN: 1674-7984; 1674-7992
• DOI: 10.1007/s11515-015-1360-4

The neurotransmitter dopamine acts via two major classes of receptors, D1-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains: L-DOPA-induced dyskinesias in Parkinson’s disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective D1-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, allosteric modulators, or by making targeted modifications to D1-receptor machinery. The development of therapies specific to D1-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.