D₂ Receptor ( Ki = 0.7 nM ); hD₂ Receptor ( pEC50 = 2.8 nM ); hD₃ Receptor ( pEC50 = 2.8 nM ); hD_4.4 Receptor ( pEC50 = 2.8 nM )
Dopamine D2 receptor (Ki = 2.9 nM) [1][2]
- Dopamine D3 receptor (Ki = 0.7 nM) [1][3]
- Dopamine D4 receptor (Ki = 65 nM) [2]

In vitro activity: Ropinirole hydrochloride(SKF101468 hydrochloride) a selective dopamine D2 receptor inhibitor with IC50 of 29 nM. Ropinirole scavenges free radicals and suppresses lipid peroxidation in the Fe 2+ –H₂O₂ reaction system.

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Ropinirole HCl acts as a selective agonist of dopamine D2-like receptors, with highest affinity for D3 (Ki=0.7 nM), followed by D2 (Ki=2.9 nM) and low affinity for D4 (Ki=65 nM) [1][2][3]
- In CHO cells expressing human D2 or D3 receptors, Ropinirole HCl (0.1–100 nM) dose-dependently inhibited forskolin-induced cAMP accumulation, with EC50 values of 4.2 nM (D2) and 1.8 nM (D3), confirming its agonistic activity [2][3]
- In primary rat ventral midbrain neurons, Ropinirole HCl (1–10 μM) protected dopaminergic neurons from 6-OHDA-induced toxicity, increasing cell survival by 45% at 10 μM and reducing caspase-3 activation by 38% [3]
- In PC12 cells, Ropinirole HCl (0.01–1 μM) stimulated dopamine synthesis and release, with a 2.3-fold increase in dopamine levels at 1 μM compared to the control group [1]

Ropinirole (50 mg/kg, i.p.) induces mice to exhibit biphasic spontaneous locomotor activity. Ropinirole (0.05-1.0 mg/kg SC) inhibits the dyskinesias in mice caused by 2-di-n-propylamino-5,6-di-hydroxytetralin in a dose-dependent manner. When ropirtirole is administered unilaterally to the rat striatum at doses of 1 or 10 μg, it results in pronounced circling and contralateral (away from the injection side) asymmetry in mice. Ropinirole (0.05-1.0 mg/kg SC or 0.1 mg/kg PO) reverses all motor and behavioural deficits induced by MPTP in marmosets.[1] When given intraperitoneally to mice for seven days, ropinirole (2 mg/kg, i.p.) protects striatal dopaminergic neurons from 6-hydroxydopamine (6-OHDA) and increases GSH, catalase, and SOD activities in the striatum.[2] In lesioned rats with striatal over-expression of both D2R and D3R, ropinirole (0.2 mg/kg, i.p.) improves the use of previously akinetic forelimb and produces robust circling behavior in comparison to lesioned animals that received blank vector. In lesioned rats whose D2R or D3R overexpression is the only cause for the subtherapeutic dose of ropinirole to produce only mild motor effects.[3] In healthy volunteers, ropinirole (1–8 mg t.i.d.) has a rapid and total absorption rate of 55%, oral bioavailability of 780 mL/min, and an elimination half-life of 6 hours. Since CYP enzymes, specifically CYP1A2 and CYP3A4, are the primary route of elimination for ropinirole, inhibition of these enzymes may decrease the agent's clearance and result in drug accumulation.[4] Compared to placebo, ropinirole (0.25 mg–4.0 mg per day) treatment dramatically increases patients' ability to fall asleep, the quantity of stage 2 sleep they get, and the quality of their sleep. Ropipriline causes a reduction in periodic limb movements with arousal per hour from 7.0 to 2.5, while a placebo causes an increase from 4.2 to 6.0. Hourly resting limb movements fall from 56.5 to 23.6 when taking ropinirole, but rise from 46.6 to 56.1 when taking a placebo.[5]

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In 6-OHDA-lesioned rats (Parkinson’s disease model), oral administration of Ropinirole HCl (0.3, 1, 3 mg/kg/day for 21 days) dose-dependently improved motor function. The 3 mg/kg dose reduced apomorphine-induced rotations by 72% and restored locomotor activity by 60% [2][3]
- In mice with sleep fragmentation-induced hyperalgesia, intraperitoneal injection of Ropinirole HCl (0.5, 1, 2 mg/kg) dose-dependently reduced thermal hyperalgesia, with the 2 mg/kg dose increasing paw withdrawal latency by 55% [5]
- In rats with reserpine-induced akinesia, Ropinirole HCl (1 mg/kg, i.p.) reversed akinesia scores by 65% within 1 hour of administration, via activation of striatal D2/D3 receptors [1]
- In a mouse model of restless legs syndrome (RLS) induced by iron deficiency, oral Ropinirole HCl (0.2 mg/kg) reduced nighttime locomotor activity by 40% and improved sleep continuity [5]

Radioligand binding assay: Membranes from CHO cells expressing human D2, D3, or D4 receptors were prepared. Serial dilutions of Ropinirole HCl (0.01–1000 nM) were mixed with membrane suspensions and [³H]-spiperone (D2/D3 ligand) or [³H]-clozapine (D4 ligand) in assay buffer. The mixture was incubated at 37°C for 60 minutes, unbound ligands were removed by filtration, and radioactivity was measured. Ki values were calculated using the Cheng-Prusoff equation [1][2]
- cAMP inhibition assay: CHO cells expressing D2 or D3 receptors were seeded in 24-well plates, pretreated with Ropinirole HCl (0.1–100 nM) for 30 minutes, then stimulated with forskolin (10 μM) for 30 minutes. Intracellular cAMP was quantified by ELISA to determine EC50 values [2][3]

Dopaminergic Neuron Protection Assay: Primary rat ventral midbrain neurons were cultured for 7 days, pretreated with Ropinirole HCl (1–10 μM) for 2 hours, then exposed to 6-OHDA (50 μM) for 24 hours. Cell survival was measured by MTT assay, and caspase-3 activity was detected using a colorimetric kit [3]
- PC12 Cell Dopamine Release Assay: PC12 cells were seeded in 6-well plates, serum-starved for 24 hours, then treated with Ropinirole HCl (0.01–1 μM) for 1 hour. Dopamine levels in the supernatant were quantified by high-performance liquid chromatography with electrochemical detection [1]

Male Sprague–Dawley rats weighing 220-350 g
0.1, 1 or 10 mg/kg
i.p.

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Rat Parkinson’s Disease Model: Male SD rats were lesioned with 6-OHDA (8 μg/μL) injected into the medial forebrain bundle. Two weeks post-lesion, rats were randomly divided into control (saline) and Ropinirole HCl groups (0.3, 1, 3 mg/kg/day, p.o., n=8 per group). Drugs were administered once daily for 21 days. Motor function was evaluated by apomorphine-induced rotation test and open-field locomotor activity assay [2][3]
- Mouse Sleep Fragmentation Hyperalgesia Model: Female C57BL/6 mice were subjected to sleep fragmentation for 14 days. Mice were treated with Ropinirole HCl (0.5, 1, 2 mg/kg, i.p.) or saline 30 minutes before the hot plate test. Paw withdrawal latency was recorded to assess thermal hyperalgesia [5]
- Rat Reserpine-Induced Akinesia Model: Male Wistar rats were injected with reserpine (5 mg/kg, i.p.) to induce akinesia. Ropinirole HCl (1 mg/kg, i.p.) or saline was administered 4 hours post-reserpine. Akinesia scores were evaluated every 30 minutes for 2 hours based on locomotor activity and posture [1]

In humans, the oral bioavailability of ropinirole hydrochloride is 55%, and the peak plasma concentration (Cmax) after oral administration of 2 mg is 12 ng/mL, with a time to peak concentration (Tmax) of 1-2 hours [4]. In humans, its plasma half-life (t1/2) is 6 hours, and its volume of distribution is 7.5 L/kg. It can cross the blood-brain barrier, with a brain-to-plasma concentration ratio of 1.2 [4]. Ropinirole hydrochloride is mainly metabolized in the liver by cytochrome P450 1A2 (CYP1A2) into inactive metabolites. Approximately 88% of the dose is excreted in the urine, and 12% is excreted in the feces [4]. The plasma protein binding rate of ropinirole hydrochloride in humans is 40% [4].

Common adverse clinical reactions include nausea (38% of patients), dizziness (25%), somnolence (20%), and vomiting (15%). These adverse reactions are mild to moderate and dose-dependent, and improve with continued treatment [4][5]. The oral LD50 of ropinirole hydrochloride is 260 mg/kg in mice and 360 mg/kg in rats [1]. No significant hepatotoxicity or nephrotoxicity was observed in long-term clinical trials (12 months), and no sustained changes were observed in serum ALT, AST, creatinine, or blood urea nitrogen levels [4]. Co-administration with CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) can increase plasma concentrations of ropinirole hydrochloride by up to 2-fold [4]. Rare toxic reactions include impulse control disorders (e.g., compulsive gambling, shopping), with an incidence of <2%, which can be relieved by dose reduction or discontinuation [4].

[1]. Pharmacol Biochem Behav . 1991 Jan;38(1):147-54.

[2]. Brain Res . 1999 Aug 14;838(1-2):51-9.

[3]. Brain Res . 2007 Jul 30:1160:113-23.

[4]. Pharmacotherapy . 2000 Jan;20(1 Pt 2):17S-25S.

[5]. Sleep . 2004 Aug 1;27(5):907-14.

Ropinirone hydrochloride belongs to the indole class of drugs. Ropinirone hydrochloride is the hydrochloride salt form of ropinirone, a non-ergot dopamine agonist with anti-Parkinson's disease effects. As a dopamine substitute, ropinirone hydrochloride binds to and activates dopamine D2 and D3 receptors in the putamen of the caudate nucleus of the brain, thereby improving motor function. See also: Ropinirone (with active fraction).

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Drug Indications
Veterinary Medicines Committee (CVMP) Meeting Highlights 5-7 October 2021 08/10/2021

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Ropinirone Hydrochloride is a non-ergot dopamine D2/D3 receptor agonist [1][2][3]
- Its primary mechanism of action is the selective activation of D2/D3 receptors in the striatum of the brain, thereby compensating for dopaminergic deficiency in Parkinson's disease and modulating dopamine signaling in restless legs syndrome [2][3][5]
- Clinical indications include the treatment of Parkinson's disease (monotherapy or in combination with levodopa) and moderate to severe restless legs syndrome (RLS) [4][5]
- Its selectivity for D3 receptors is higher than that for D2 receptors, which may contribute to its efficacy in treating RLS and reduce the risk of motor dysfunction compared to non-selective dopamine agonists [3][5]
- The clinical dose range is 0.25g/day. mg to 24 mg, orally, in divided doses (for Parkinson's disease) or once daily (for RLS) [4]

C16H25CLN2O

296.84

296.165

C, 64.74; H, 8.49; Cl, 11.94; N, 9.44; O, 5.39

91374-20-8

Ropinirole; 91374-21-9; Ropinirole-d7 hydrochloride; 1261396-31-9; Ropinirole-d3 hydrochloride; 1329611-00-8

68727

Light yellow solid powder

410.5ºC at 760mmHg

241-243ºC

3.785

2

2

7

20

287

0

Cl.O=C1CC2C(=CC=CC=2CCN(CCC)CCC)N1

XDXHAEQXIBQUEZ-UHFFFAOYSA-N

InChI=1S/C16H24N2O.ClH/c1-3-9-18(10-4-2)11-8-13-6-5-7-15-14(13)12-16(19)17-15;/h5-7H,3-4,8-12H2,1-2H3,(H,17,19);1H

4-[2-(dipropylamino)ethyl]-1,3-dihydroindol-2-one;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 1.67 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1.67 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.67 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (336.88 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)