Emerging research on D1/D5 receptor selectivity in Parkinson's disease (PD)
Understanding D1/D5 receptor selectivity
D1 RECEPTOR1,2
Most abundant of the 5 dopamine receptors in the CNS and plays a crucial role in movement, reward, and cognitive functions (eg, attention, memory)
D5 RECEPTOR1-3
Modulates motor activity and cognitive functions (eg, decision-making)
Current oral PD treatment approaches pose significant challenges for patients and healthcare providers3-6
Oral carbidopa/levodopa (CD/LD) loses efficacy over time due to disease progression and its short half-life, and patients often require more frequent and/or higher doses, which can lead to dyskinesia
D2/D3/D4 agonists are associated with adverse effects such as impulse control disorders, somnolence, hallucinations, and edema, creating additional burden for patients
Despite nearly 4 decades of investigation, no centrally acting D1/D5 receptor compounds are currently approved for clinical use
Research into D1/D5 receptor selectivity is ongoing
Interested in learning more about D1/D5 selectivity? Contact your local Medical Science Liaison (MSL) for more information
CNS=central nervous system.
References: 1. Bhatia A, Lenchner JR, Saadabadi A. Biochemistry, Dopamine Receptors. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 22, 2023. 2. Mishra A, Singh S, Shukla S. Physiological and functional basis of dopamine receptors and their role in neurogenesis: possible implication for Parkinson's disease. J Exp Neurosci. 2018;12:1179069518779829. doi:10.1177/1179069518779829 3. Isaacson SH, Hauser RA, Pahwa R, Gray D, Duvvuri S. Dopamine agonists in Parkinson's disease: impact of D1-like or D2-like dopamine receptor subtype selectivity and avenues for future treatment. Clin Park Relat Disord. 2023;9:100212. doi:10.1016/j.prdoa.2023.100212 4. Ellis JM, Fell MJ. Current approaches to the treatment of Parkinson’s disease. Bioorg Med Chem Lett. 2017;27(18):4247-4255. doi:10.1016/j.bmcl.2017.07.075 5. Poewe W, Mahlknecht P. Pharmacologic treatment of motor symptoms associated with Parkinson disease. Neurol Clin. 2020;38(2):255-267. doi:10.1016/j.ncl.2019.12.002 6. Jones-Tabah J, Mohammad H, Paulus EG, Clarke PBS, Hébert TE. The signaling and pharmacology of the dopamine D1 receptor. Front Cell Neurosci. 2022;15:806618. doi:10.3389/fncel.2021.806618