Rotigotine is a nonergoline dopamine receptor agonist with structural similarity to dopamine. Rotigotine binds to the D1 through D5 dopamine receptors, having several times more affinity than dopamine does to the D2 and D3 receptors. Rotigotine's high lipid solubility and extended duration of action when applied to the skin in experimental models of PD suggested that rotigotine was a candidate for transdermal application.Randomized clinical studies also have demonstrated the efficacy of rotigotine in improving the symptoms of moderate-to-severe primary RLS.Rotigotine provides minor protection against MPP⁺ and rescues a significant number of THir neurons against rotenone in primary mesencephalic cell cultures relevant to PD.
|Source||Bioanalysis (2014). Figure 3. Rotigotine|
|Method||competition binding assays|
|Cell Lines||LMtk cells|
|Results||There was a good correlation between functional potency of the agonists examined (Table 4) and their binding affinity versus [3H]rotigotine (Table 5) at the three dopamine receptors|
|Source||Bioanalysis (2014). Figure 2. Rotigotine|
|Method||competition binding assays|
|Cell Lines||CHO cells|
|Results||Equilibrium saturation assays were performed in triplicate with [3H]rotigotine and with the radiolabelled antagonist [3H]SCH23390 for D1 and D5, [3H]raclopride for D2 and [3H]spiperone for D3 and D4 receptors|
|Cell lines||primary mesencephalic cell|
|Preparation method||To investigate the effect of rotigotine (UCB, Belgium) on the survival of THir neurons, primary mesencephalic cell cultures were treated with different concentrations of rotigotine (0.01, 0.1, 1 and 10 µM) from the 6th DIV for 8 consecutive days. Rotigotine was added with each change of the culture medium every second day from a fresh stock solution (10 mM) prepared in DMSO (0.1% final concentration). To investigate the effect of rotigotine against MPP+ or rotenone-induced cell death, rotigotine was added from the 6th DIV until the 14th DIV as described above and MPP+ (10 µM) or rotenone (20 nM) were co-administered on the 12th DIV for 48 h.|
|Concentrations||0.01, 0.1, 1 and 10 μM|
|Incubation time||48 h|
|Animal models||Sprague-Dawley rats|
|Formulation||1:10 ratio of dimethyl sulfoxide (DMSO) and 5% dextrose|
|Dosages||0.5 or 3 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 10 mM|
Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson's disease and restless legs syndrome.
Benitez A, et al. Ann N Y Acad Sci. 2014 Aug 21. PMID: 25145951.
Neuroprotective effect of rotigotine against complex I inhibitors, MPP⁺ and rotenone, in primary mesencephalic cell culture.
Radad K, et al. Folia Neuropathol. 2014;52(2):179-86. PMID: 25118903.
|Related Dopamine Receptor Products|
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SCH23390 is a potent dopamine receptor antagonist (Ki values are 0.2 nM and 0.3 nM at D1 and D5 receptor sub-types, respectively).
MPTP hcl is a compound to the neurotoxin MPP+ which causes permanent symptoms of Parkinson's disease.
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6-Hydroxydopamine hydrochloride is an antagonist of the neurotransmitter dopamine.
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