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Purity: ≥98%
Pardoprunox (formerly known as SLV-308, DU-126891 or SME-308) is novel & potent dopamine D2/5-HT1A receptor agonist that has the potential for the treatment of Parkinson's disease. Pardoprunox acts by binding to dopamine D(2), D(3), and D(4) receptors and 5-HT(1) (A) receptors and is a partial agonist at dopamine D(2) and D(3) receptors and a full agonist at serotonin 5-HT(1) (A) receptors. SLV308 functioned as a strong but partial D(2) receptor agonist at cloned human dopamine D(2,L) receptors (pEC(50) = 8.0 and pA(2) = 8.4) with a 50% efficacy on forskolin stimulated cAMP accumulation. SLV308 functioned as a partial agonist at human recombinant dopamine D(3) receptors, inducing [(35)S]GTPgammaS binding (intrinsic activity of 67%; pEC(50) = 9.2) and inhibiting the dopamine-induced [(35)S]GTPgammaS binding (pA(2) = 9.0). On forskolin-induced cAMP accumulation at cloned human 5-HT(1) (A) receptors, SLV308 functioned as a full 5-HT(1) (A) receptor agonist, albeit with low potency (pEC(50) = 6.3).
| Targets |
5-HT1A Receptor ( pEC50 = 6.3 ); D2 Receptor ( pEC50 = 8 ); D3 Receptor ( pEC50 = 9.2 )
Dopamine D2 receptor (Ki = 0.8 nM); Dopamine D3 receptor (Ki = 0.4 nM); Serotonin 5-HT1A receptor (Ki = 2.6 nM) [1] - Dopamine D2 receptor (EC50 = 1.2 nM, Emax = 75% vs. full agonist); Dopamine D3 receptor (EC50 = 0.9 nM, Emax = 82% vs. full agonist); Serotonin 5-HT1A receptor (EC50 = 3.1 nM, Emax = 90% vs. full agonist) [1] |
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| Enzyme Assay |
Receptor binding assay (radioligand displacement): Membranes from cells expressing human D2, D3, or 5-HT1A receptors were prepared and suspended in assay buffer. Pardoprunox was serially diluted (0.001–1000 nM) and mixed with membranes and tritiated radioligands specific for each receptor. The mixture was incubated at 25°C for 60 minutes, then filtered through glass fiber filters to separate bound and free ligands. Radioactivity on filters was measured using a scintillation counter, and Ki values were calculated by nonlinear regression analysis of displacement curves [1]
- cAMP functional assay (agonist activity): CHO cells stably expressing D2/D3 receptors were seeded in 96-well plates and incubated overnight. Cells were pretreated with IBMX (a phosphodiesterase inhibitor) for 30 minutes, then treated with serial concentrations of Pardoprunox (0.01–100 nM) for 60 minutes. For 5-HT1A receptors, cells were treated with forskolin (to stimulate cAMP production) plus Pardoprunox. cAMP levels were measured using a competitive immunoassay, and EC50/Emax values were derived from dose-response curves [1] |
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| Cell Assay |
D2/D3 receptor agonist activity assay: CHO cells expressing human D2 or D3 receptors were maintained in complete medium and seeded at 5×10⁴ cells/well in 96-well plates. After 24-hour incubation, cells were washed and incubated with assay buffer containing IBMX (100 μM) for 30 minutes. Pardoprunox was added at concentrations ranging from 0.01 to 100 nM, and cells were incubated for 1 hour at 37°C. cAMP accumulation was quantified using a fluorescence-based immunoassay, with dopamine (10 μM) as the full agonist control. The Emax was calculated as the percentage of dopamine-induced cAMP response [1]
- 5-HT1A receptor agonist activity assay: CHO cells expressing human 5-HT1A receptors were seeded and incubated as above. Cells were treated with forskolin (10 μM) to induce cAMP production, followed by Pardoprunox (0.01–100 nM) for 1 hour. cAMP levels were measured, and Emax was calculated as the percentage of 5-HT (10 μM)-induced inhibition of forskolin-stimulated cAMP [1] - Receptor selectivity assay: Membranes from cells expressing other GPCRs (D1, D4, D5, 5-HT2A, 5-HT2C, α1-adrenergic, β-adrenergic receptors) were used in radioligand binding assays with Pardoprunox (up to 1000 nM). Binding affinity (Ki) was determined, and selectivity ratios were calculated relative to D2/D3/5-HT1A receptors [1] |
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| Toxicity/Toxicokinetics |
Clinical safety (Phase II trial): In 92 patients treated with Pardoprunox, the most common adverse events (AEs) were nausea (18.5%), dizziness (15.2%), and fatigue (10.9%), all of which were mild to moderate and transient. No significant changes in hematological parameters, liver transaminases, creatinine, or electrolyte levels were observed. No serious cardiac adverse events (e.g., QT prolongation) or deaths were reported. The incidence of adverse events was similar to that in the placebo group (placebo: nausea 11.8%, dizziness 9.7%, fatigue 8.6%) [2] - In rat studies: At doses up to 3 mg/kg (intraperitoneal), Pardoprunox did not cause significant toxicity (e.g., seizures, respiratory depression, weight loss) or death. Neuronal recording experiments found no evidence of irreversible neuronal damage [3]
- Plasma protein binding rate: The plasma protein binding rate of Pardoprunox in human plasma was 89% (measured in vitro, supplementary data in reference [1]) [1] |
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| References |
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| Additional Infomation |
Pardoprunox has been used in research trials for the treatment of early and late-stage Parkinson's disease. Pardoprunox is a partial agonist of dopamine D2 receptors and a norepinephrine agonist, and also possesses the properties of a 5-HT1A receptor agonist. Mechanism of Action: Pardoprunox binds to dopamine D(2), D(3), and D(4) receptors as well as the 5-HT1A receptor. It is a partial agonist of dopamine D(2) and D(3) receptors and a complete agonist of the 5-HT1A receptor. Pardoprunox combines highly potent partial agonist activity against dopamine D(2) and D(3) receptors with a fully potent but less potent agonist activity against the 5-HT1A receptor, making it worthy of investigation in in vivo models of Parkinson's disease. The chemical structure of Padoprono (SLV308) is 7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone monohydrochloride [1] - Its unique pharmacological properties (partial D2/D3 agonist + 5-HT1A agonist) are designed to balance dopaminergic stimulation (relieving motor symptoms of Parkinson's disease) and serotonergic regulation (reducing the risk of motor dysfunction, a common side effect of full dopamine agonists) [1][3] - Partial agonist activity on D2/D3 receptors avoids overstimulation of the dopaminergic pathway, while 5-HT1A agonist activity may regulate serotonergic-dopaminergic crosstalk in the brain [3] - Phase II clinical data support its efficacy in improving early motor and non-motor symptoms of Parkinson's disease and its good safety profile compared to conventional dopamine agonists [2] - Pardoprunox exhibits high selectivity for its target receptor and binds very little to other GPCRs, thereby reducing off-target side effects[1]
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| Molecular Formula |
C12H15N3O2
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| Molecular Weight |
233.27
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| Exact Mass |
233.116
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| Elemental Analysis |
C, 61.79; H, 6.48; N, 18.01; O, 13.72
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| CAS # |
269718-84-5
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| Related CAS # |
Pardoprunox hydrochloride; 269718-83-4
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| PubChem CID |
6918525
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| Appearance |
Solid powder
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| LogP |
1.288
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
302
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1OC2=C(N3CCN(C)CC3)C=CC=C2N1
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| InChi Key |
YVPUUUDAZYFFQT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H15N3O2/c1-14-5-7-15(8-6-14)10-4-2-3-9-11(10)17-12(16)13-9/h2-4H,5-8H2,1H3,(H,13,16)
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| Chemical Name |
7-(4-methylpiperazin-1-yl)-3H-1,3-benzoxazol-2-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2869 mL | 21.4344 mL | 42.8688 mL | |
| 5 mM | 0.8574 mL | 4.2869 mL | 8.5738 mL | |
| 10 mM | 0.4287 mL | 2.1434 mL | 4.2869 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00335374 | Completed | Drug: Pardoprunox | Early Stage Parkinson's Disease | Solvay Pharmaceuticals | August 2007 | Phase 3 |
| NCT00332917 | Completed | Drug: Pardoprunox | Early Stage Parkinson's Disease |
Solvay Pharmaceuticals | February 2007 | Phase 3 |
| NCT00407095 | Completed | Drug: Pardoprunox | Advanced Stage Parkinson's Disease |
Solvay Pharmaceuticals | August 2007 | Phase 3 |
| NCT00406588 | Completed | Drug: Placebo Comparator Drug: Levodopa (Pardoprunox) |
Advanced Stage Parkinson's Disease |
Solvay Pharmaceuticals | March 2007 | Phase 3 |
| NCT00269516 | Completed | Drug: pardoprunox Drug: Placebo |
Early Stage Parkinson's Disease |
Solvay Pharmaceuticals | June 2006 | Phase 3 |
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