Ropinirole HCl is a non-ergoline dopamine receptor (D2/D3/D4) agonist (pEC50=7.4, 8.4, 6.8). Ropinirole HCl activates postsynaptic D2-like receptors in the striatum and stimulates D3 receptors to compensate for insufficient dopaminergic transmission. Ropinirole HCl inhibits prolactin secretion. Ropinirole HCl is commonly used in research on Parkinson's disease and restless legs syndrome[1-4].
In vitro, treatment of SH-SY5Y cells with 10μM Ropinirole HCl for 2h altered the gene expression profile and upregulated the expression of genes including PIK3C2B and EPS15[5]. Treatment of HEK293 cells with Ropinirole HCl-loaded P407/Tw80/MβCD and P407/Tw80/HPβCD hybrid systems at 25-500μg/mL for 2h reduced the viability of HEK293 cells[6]. Treatment of HEK293 cells with 20-100μM Ropinirole HCl for 24h increased LC3-II expression levels in HEK293 cells[7].
In vivo, a single intraperitoneal injection of 1mg/kg Ropinirole HCl promoted sevoflurane anesthesia emergence in mice with vlPAGGABA-VTA induction[8]. A single intracerebral injection of Ropinirole HCl (200nL; 1μM) into the dopamine D2-like receptor-containing brain region from the substantia nigra reticulata projection to the subthalamic nucleus elevated the contralateral mechanical pain threshold in neuropathic pain mice. A single intracerebral injection of Ropinirole HCl (0.3μg; 200nL) into the subthalamic nucleus elevated the contralateral mechanical pain threshold and elevated bilateral thermal pain thresholds in 6-hydroxydopamine Parkinson's disease mice[9]. A single intraperitoneal injection of 1-10mg/kg Ropinirole HCl reduced immobility time in the forced swim test and tail suspension test in Laca mice[10].
References:[1] Eden R J, Costall B, Domeney A M, et al. Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav. 1991;38(1):147-154.
[2] Iida M, Miyazaki I, Tanaka K, et al. Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res. 1999 May 8;838(1-2):51-59.
[3] Pardeshi C V, Belgamwar V S, Tekade A R, et al. Novel surface modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation. J Mater Sci: Mater Med. 2013;24(7):2101-2115.
[4] Saitani E-M, Papakyriakopoulou P, Damalas D, et al. Pharmacokinetic evaluation of intranasal ropinirole delivery using hybrid polymer/surfactant/βCD systems in C57BL/6J mice. Int J Pharm. 2026;697:126855.
[5] Zhu MZ, Le WD, Jin G, et al. Ropinirole alters gene expression profiles in SH-SY5Y cells: a whole genome microarray study. Braz J Med Biol Res. 2016 Feb;49(2):e4857.
[6] Saitani, E.-M.; Pippa, N.; Perinelli, D.R., et al. Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation. Int. J. Mol. Sci. 2024, 25, 1162.
[7] Li N, Rao L, Zhao X, et al. Chlorpromazine affects autophagy in association with altered Rag GTPase-mTORC1-TFEB signaling. Front Cell Dev Biol. 2023 Sep 8;11:1266198.
[8] Zhong C-C, Xu Z, Gan J, et al. Acute Ongoing Nociception Delays Recovery of Consciousness from Sevoflurane Anesthesia via a Midbrain Circuit. J Neurosci. 2024 Aug 21;44(34):e0740242024.
[9] Ji Y, Li S, Zhang J, et al. Nigra-Subthalamic Dopaminergic Circuitry Modulates and Represents Distinct Pain Modality in Physiological and Pain States in Mice. Adv Sci (Weinh). 2026;13:e19913.
[10] Dhir A, Kulkarni S K, et al. Involvement of dopamine(DA)/serotonin(5-HT)/sigma(σ) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist. Brain Res Bull. 2007;74(1):58-65.