Ropinirole HCl (formerly SKF 101468; SKF-101468A; SKF 101468A; Requip), the hydrochloride salt of ropinirole, is a potent and selective dopamine D2 receptors agonist ( Ki = 29 nM) of the non-ergoline class of medications used for PD-Parkinson's disease, RLS/restless legs syndrome and extrapyramidal symptoms. It can also lessen the negative effects of selective serotonin reuptake inhibitors (SSRIs) and antipsychotics, such as Parkinsonism syndrome, erectile dysfunction, and sexual dysfunction. In the Fe2+-H2O2 reaction system, ropinirole scavenges free radicals and inhibits lipid peroxidation.

Physicochemical Properties

Molecular Formula	C16H25CLN2O
Molecular Weight	296.84
Exact Mass	296.165
Elemental Analysis	C, 64.74; H, 8.49; Cl, 11.94; N, 9.44; O, 5.39
CAS #	91374-20-8
Related CAS #	Ropinirole; 91374-21-9; Ropinirole-d7 hydrochloride; 1261396-31-9; Ropinirole-d3 hydrochloride; 1329611-00-8
PubChem CID	68727
Appearance	Light yellow solid powder
Boiling Point	410.5ºC at 760mmHg
Melting Point	241-243ºC
LogP	3.785
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	7
Heavy Atom Count	20
Complexity	287
Defined Atom Stereocenter Count	0
SMILES	Cl.O=C1CC2C(=CC=CC=2CCN(CCC)CCC)N1
InChi Key	XDXHAEQXIBQUEZ-UHFFFAOYSA-N
InChi Code	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
Chemical Name	4-[2-(dipropylamino)ethyl]-1,3-dihydroindol-2-one;hydrochloride
Synonyms	SKF-101468A; Ropinirole Hydrochloride; Ropinirole HCl; UNII-D7ZD41RZI9; SK and F 101468; SK and F-101,468; SKF 101468;SKF101468A; SKF 101468A
HS Tariff Code	2934.99.9001
Storage	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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	D2 Receptor ( Ki = 0.7 nM ); hD2 Receptor ( pEC50 = 2.8 nM ); hD3 Receptor ( pEC50 = 2.8 nM ); hD4.4 Receptor ( pEC50 = 2.8 nM )
ln Vitro	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 Fe2+–H2O2 reaction system.
ln Vivo	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]
Animal Protocol	Male Sprague–Dawley rats weighing 220-350 g 0.1, 1 or 10 mg/kg i.p.
References	[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.
Additional Infomation	Ropinirole hydrochloride is a member of indoles. Ropinirole Hydrochloride is the hydrochloride salt form of ropinirole, a non-ergot dopamine agonist with antiparkinsonian property. Acting as a substitute for dopamine, ropinirole hydrochloride binds to and activates dopamine D2 and D3 receptors within the caudate putamen in the brain, thereby improving motor function. See also: Ropinirole (has active moiety). Drug Indication Meeting highlights from the Committee for Medicinal Products for Veterinary Use (CVMP) 5-7 October 202108/10/2021

Solubility Data

Solubility (In Vitro)

DMSO: 10~16.7 mg/mL (33.7~56.2 mM) Water: 30~60 mg/mL (101.1~202.1 mM) Ethanol: <1 mg/mL

Solubility (In Vivo)

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.3688 mL	16.8441 mL	33.6882 mL
	5 mM	0.6738 mL	3.3688 mL	6.7376 mL
	10 mM	0.3369 mL	1.6844 mL	3.3688 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.