rac-Rotigotine Hydrochloride 102120-99-0_Dopamine Receptor_GPCR & G Protein_Signaling Pathways_Products

rac-Rotigotine Hydrochloride is the racemic mixture of Rotigotine (N-0437; N-0923), which is a potent, non-selective and dopamine receptor full agonist, used in the treatment of Parkinson's disease and restless legs syndrome. Rotigotine s an agonist of the dopamine D2 and D3 receptors, with corresponding Ki values of 13 and 0.71 nM for D2 and D3. Rotagotine also shows a high affinity for 5-HT1A and adrenergic α2B receptors.

Physicochemical Properties

Molecular Formula	C19H26CLNOS
Molecular Weight	351.93
Exact Mass	351.142
CAS #	102120-99-0
Related CAS #	(Rac)-Rotigotine-d3 hydrochloride; 1215846-20-0; (Rac)-Rotigotine; 92206-54-7; (Rac)-Rotigotine-d7 hydrochloride
PubChem CID	6917969
Appearance	Solid powder
LogP	5.067
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	6
Heavy Atom Count	23
Complexity	337
Defined Atom Stereocenter Count	0
InChi Key	CEXBONHIOKGWNU-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H25NOS.ClH/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21;/h3-7,13,16,21H,2,8-12,14H2,1H3;1H
Chemical Name	6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol;hydrochloride
Synonyms	N 0923; N-0923; N-0924 Rotigotine Hydrochloride; Rotigotine HCl Neupro
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

D₃ Receptor ( Ki = 0.71 nM ); D₂ Receptor ( Ki = 13.5 nM ); D₄ Receptor ( Ki = 3.9-15 nM ); D₅ Receptor ( Ki = 5.4 nM ); D₁ Receptor ( Ki = 83 nM nM ); 5-HT_1A Receptor ( Ki = 30 nM ); 5-HT_2B Receptor ( Ki = 27 nM ); Alpha-2B adrenergic receptor

ln Vitro

In vitro activity: Rotigotine exhibits a 100-fold selectivity when compared to D1 receptors (pKi=7.2) and a 10-fold selectivity for D3 (pKi=9.2) receptors when compared with D2, D4, and D5 (pKi=8.5-8.0). Rotigotine exhibits full agonistic behavior at all dopamine receptors in functional studies; however, it is noteworthy that the potency of D1 receptor stimulation is comparable to that of D2 and D3 receptors (pEC50: 9.0, 9.4-8.6, 9.7)[1].
In primary mesencephalic cell culture, rotigotine (10 µM) reduces the number of THir neurons by forty percent. Rotigotine (0.01 µM) significantly inhibits rotenone-induced ROS production, significantly protects dopaminergic neurons against MPP+ toxicity, and mildly protects dopaminergic neurons against rotenone-induced cell death[4].

ln Vivo

Rotigotine (N-0437; N-0923; 0.035, 0.1, and 0.35 mg/kg) dose-dependently produces contralateral turning behavior in primed rats. Compared to primed rats, drug-naive rats exhibit less turning behavior when Rotigotine, either by itself or in conjunction with SCH 39166, is administered.

Enzyme Assay

In 96-well polypropylene tubes, binding assays are carried out with a final volume of 2 mL for D1 and D4 membranes and 1 mL for D2, D3, and D5 membranes. These tubes contain the following materials: 50 μL radioligand, 10 μL drug/buffer/non-specific binding, buffer (final concentration 50 mM Tris-HCl pH 7.4, MgCl2 2 mM), and membranes (5 μg protein for D2 and D3 and 25 μg protein for D1 and D5). Rapid vacuum filtration through A/C glass fiber filters presoaked in 0.1% polyethylenimine is used to determine bound radioligand after 120 minutes of incubation at 25°C. Liquid scintillation counting is used to determine the retained radioactivity after the filters are four times cleaned with 2 mL of ice-cold ishing buffer (Tris-HCl 50 mM, pH 7.4 at 4°C).

Animal Protocol

Two weeks following the 6-OHDA lesions, rats receive a 0.5 mg/kg s.c. apomorphine priming. Rats that perform fewer than 150 contralateral rotations in the course of the one-hour testing session are not included in the research. After priming, rats are split into three experimental groups and given varying dosages of dopamine receptor agonists (pramipexole or rotigotine), either by themselves or in conjunction with dopamine D₁ (SCH 39166) or D₂ (eticlopride) receptor antagonists, as previously reported: saline+Rotigotine (0.035 mg/kg s.c., n=9; 0.1 mg/kg s.c., n=9; 0.35 mg/kg s.c., n=8); SCH 39166 (0.1 mg/kg s.c.)+Rotigotine (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5); eticlopride (0.1 mg/kg s.c.) + Rotigotine (0.1 mg/kg s.c., n=5; 0.35 mg/kg s.c., n=5); Saline+pramipexole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=12; 0.35 mg/kg s.c., n=7); SCH 39166 (0.1 mg/kg s.c.)+pramipexole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=6; 0.35 mg/kg s.c., n=6); eticlopride (0.1 mg/kg s.c.)+pramipexole (0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5).

Rats

References

[1]. Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol. 2015 Feb;172(4):1124-35.

[2]. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):73-86.

[3]. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors. Eur J Pharmacol. 2016 Oct 5;788:183-91.

[4]. Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencephalic cell culture. Folia Neuropathol. 2014;52(2):179-86.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 50 mg/mL (~142.1 mM)
H2O: < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.10 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 25.0 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: ≥ 2.5 mg/mL (7.10 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 25.0 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: ≥ 2.5 mg/mL (7.10 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8415 mL	14.2074 mL	28.4147 mL
	5 mM	0.5683 mL	2.8415 mL	5.6829 mL
	10 mM	0.2841 mL	1.4207 mL	2.8415 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.

PeptideDB

rac-Rotigotine Hydrochloride 102120-99-0

CAS No.: 102120-99-0

Physicochemical Properties

Biological Activity

Solubility Data