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Purity: ≥98%
Pramipexole (also known as SND 919; (S)-Pramipexole), an agonist of the Gαi-linked dopamine receptors D2, D3, and D4, is a potent dopamine agonist of the non-ergoline class. It is used to treat restless legs syndrome (RLS) and Parkinson's disease (PD). Pramipexole exhibits negligible affinity (500-10,000 nM) towards the α2-adrenergic receptor, 5-HT1A, 5-HT1B, and 5-HT1D. A partial/full agonist of the D2S, D2L, D3, and D4 receptor, pramipexole has a Ki of 3.9, 2.2, 0.5, and 5.1 nM for the D2S, D2L, D3, and D4 receptors, respectively.
| Targets |
D2 Receptor ( Ki = 3.9 nM ); D3 Receptor ( Ki = 0.5 nM ); D4 Receptor ( Ki = 1.3 nM )
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| ln Vitro |
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| Enzyme Assay |
The blood-brain barrier (BBB) transport of pramipexole, a potent dopamine receptor agonist with high efficacy for Parkinson's disease, was mainly characterized using immortalized rat brain capillary endothelial cells (RBEC)1 as an in vitro BBB model. [(14)C]Pramipexole uptake by RBEC1 was dependent on temperature and pH, but not sodium ion concentration or membrane potential. The uptake was inhibited by several organic cations including pyrilamine. Mutual inhibition was observed between pramipexole and pyrilamine. In addition, [(14)C]pramipexole uptake was stimulated by preloading unlabeled pramipexole. RT-PCR analysis for organic cation transporters (rOCT1-3, rOCTN1-2) in RBEC1 was performed. The mRNA level of rOCTN2 was the highest, followed by rOCTN1, while expression of rOCT1, rOCT2 and rOCT3 was negligible. The brain uptake of [(14)C]pramipexole, which was measured by the in situ rat brain perfusion technique, was significantly inhibited by unlabeled pramipexole. These results suggest that pramipexole is, at least in part, transported across the BBB by an organic cation-sensitive transporter. The pramipexole transport in RBEC1 was pH-dependent, but sodium- and membrane potential-independent[2].
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| Cell Assay |
The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs). Two hiPSC clones from healthy donors were differentiated into midbrain DA neurons. Ropinirole and pramipexole produced dose-dependent increases of dendritic arborization and soma size after 3 days of culture, effects antagonized by the selective D3R antagonists SB277011-A and S33084 and by the mTOR pathway kinase inhibitors LY294002 and rapamycin. All treatments were also effective in attenuating the D3R-dependent increase of p70S6-kinase phosphorylation. Immunoneutralisation of BDNF, inhibition of TrkB receptors, and blockade of MEK-ERK signaling likewise prevented ropinirole-induced structural plasticity, suggesting a critical interaction between BDNF and D3R signaling pathways. The highly similar profiles of data acquired with DA neurons derived from two hiPSC clones underpin their reliability for characterization of pharmacological agents acting via dopaminergic mechanisms[3].
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| Animal Protocol |
Male Wistar rats weighing 250-300 g (16-18 weeks old)
0.25 mg/kg, 1 mg/kg Intraperitoneal injection A dopamine D2 receptor agonist, pramipexole, has been found to elicit neuroprotection in patients with Parkinson's disease and restless leg syndrome. Recent evidence has shown that pramipexole mediates its neuroprotection through mitochondria. Considering this, we examined the possible mitochondrial role of pramipexole in promoting neuroprotection following an ischemic stroke of rat. Male Wistar rats underwent transient middle cerebral artery occlusion (tMCAO) and then received pramipexole (0.25 mg and 1 mg/kg body weight) at 1, 6, 12 and 18 h post-occlusion. A panel of neurological tests and 2,3,5-triphenyl tetrazolium chloride (TTC) staining were performed at 24 h after the surgery. Flow cytometry was used to detect the mitochondrial membrane potential, and mitochondrial levels of reactive oxygen species (ROS) and Ca2+, respectively. Mitochondrial oxidative phosphorylation was analyzed by oxygraph (oxygen electrode). Western blotting was used to analyze the expression of various proteins such as Bax, Bcl-2 and cytochrome c Pramipexole promoted the neurological recovery as shown by the panel of neurobehavioral tests and TTC staining. Post-stroke treatment with pramipexole reduced levels of mitochondrial ROS and Ca2+ after ischemia. Pramipexole elevated the mitochondrial membrane potential and mitochondrial oxidative phosphorylation. Western blotting showed that pramipexole inhibited the transfer of cytochrome c from mitochondria to cytosol, and hence inhibited the mitochondrial permeability transition pore. Thus, our results have demonstrated that post-stroke administration of pramipexole induces the neurological recovery through mitochondrial pathways in ischemia/reperfusion injury[5]. |
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| Additional Infomation |
Pramipexole is a member of the class of benzothiazoles that is 4,5,6,7-tetrahydro-1,3-benzothiazole in which the hydrogens at the 2 and 6-pro-S-positions are substituted by amino and propylamino groups, respectively. It has a role as an antiparkinson drug, a dopamine agonist, an antidyskinesia agent and a radical scavenger. It is a member of benzothiazoles and a diamine. It is a conjugate base of a pramipexole(2+).
Pramipexole is a drug used to treat the symptoms of Parkinson's Disease (PD). It is a non-ergot dopamine agonist drug that is efficacious in treating various Parkinson's symptoms such as tremor, rigidity, and bradykinesia (slow movement). It was first approved by the FDA in 1997. Parkinson's Disease is one of the most common neurodegenerative disorders and causes a high level of disability in patients, leading to increased difficulty in performing activities of daily living due to symptoms that progress over time. The prevalence of Parkinson's Disease worldwide has increased from approximately 2.5 million in 1990 to about 6.1 million in 2016. This increase may be attributed to an aging population along with other contributing factors. In addition to the above FDA approval for Parkinson's Disease, pramipexole was also approved by the FDA in 2006 for the treatment of Restless Legs Syndrome (RLS). RLS is a sleep-related disorder characterized by unpleasant sensations in the lower extremities, often accompanied by an uncontrollable urge to move the legs. View More
Pramipexole is a Nonergot Dopamine Agonist. The mechanism of action of pramipexole is as a Dopamine Agonist.
Absorption: The bioavailability of pramipexole is higher than 90%, indicating a high level of absorption. Route of Elimination: The main route of pramipexole elimination, with 90% of a pramipexole dose found in the urine, almost entirely as unchanged drug. Volume of Distribution: This drug is extensively distributed in the body with a volume of distribution of approximately 500 L. Clearance: Renal clearance is about 400 mL/min, indicating heavy secretion by the renal tubules. Pramipexole is extensively distributed, having a volume of distribution of about 500 L. Protein binding is less than 20% in plasma; with albumin accounting for most of the protein binding in human serum. Pramipexole distributes into red blood cells as indicated by an erythrocyte to plasma ratio of approximately 2.0 and a blood to plasma ratio of approximately 1.5. Consistent with the large volume of distribution in humans, whole body autoradiography and brain tissue levels in rats indicated that pramipexole was widely distributed throughout the body, including the brain. Biological Half-Life: About 8.5-12 hours. The terminal elimination half-life was about 8.5 hours in young volunteers (mean age 30 years) and about 12 hours in elderly volunteers (mean age 70 years). The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptors. Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes. The clinical significance of this binding specificity is unknown. The purpose of this study was to determine the binding sites of pramipexole in extrastriatal dopaminergic regions because its antidepressive effects have been speculated to occur by activating the dopamine D(2) receptor subfamily in extrastriatal areas. Dynamic positron emission tomography (PET) scanning using (11)C-FLB 457 for quantification of D(2)/D(3) receptor subtype was performed on 15 healthy volunteers. Each subject underwent two PET scans before and after receiving a single dose of pramipexole (0, 0.125, or 0.25 mg). The study demonstrated that pramipexole significantly binds to D(2)/D(3) receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus at a dose of 0.25 mg. These regions have been indicated to have some relation to depression and may be part of the target sites where pramipexole exerts its antidepressive effects. Pramipexole dihydrochloride, a synthetic benzothiazolamine derivative, is a nonergot-derivative dopamine receptor agonist. In in vitro binding studies, pramipexole demonstrated high binding specificity for and intrinsic activity at dopamine D2 receptors compared with other dopamine receptor agonists (e.g., bromocriptine, pergolide), having a higher affinity for the D3 receptor subtype than for the D2 or D4 subtypes. Pramipexole binds with moderate affinity to alpha2-adrenergic receptors but has little or no affinity for alpha1- or beta-adrenergic, acetylcholine, dopamine D1, or serotonin (5-hydroxytryptamine (5-HT)) receptors. |
| Molecular Formula |
C10H17N3S
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| Molecular Weight |
211.33
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| Exact Mass |
211.11
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| Elemental Analysis |
C, 56.84; H, 8.11; N, 19.88; S, 15.17
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| CAS # |
104632-26-0
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| Related CAS # |
Pramipexole dihydrochloride; 104632-25-9; Dexpramipexole dihydrochloride; 104632-27-1; Pramipexole dihydrochloride hydrate; 191217-81-9; Dexpramipexole;104632-28-2; Pramipexole-d5; 1217975-28-4
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| PubChem CID |
119570
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
378.0±42.0 °C at 760 mmHg
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| Melting Point |
288-290°C
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| Flash Point |
182.4±27.9 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.583
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| LogP |
1.42
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| tPSA |
79.18
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| SMILES |
CCCN[C@H]1CCC2=C(C1)SC(=N2)N
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| InChi Key |
FASDKYOPVNHBLU-ZETCQYMHSA-N
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| InChi Code |
InChI=1S/C10H17N3S/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8/h7,12H,2-6H2,1H3,(H2,11,13)/t7-/m0/s1
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| Chemical Name |
(6S)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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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) |
Solubility in Formulation 1: 10 mg/mL (47.32 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.83 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.83 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7319 mL | 23.6597 mL | 47.3194 mL | |
| 5 mM | 0.9464 mL | 4.7319 mL | 9.4639 mL | |
| 10 mM | 0.4732 mL | 2.3660 mL | 4.7319 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 |
| NCT04759703 | Recruiting | Drug: Pramipexole Drug: Placebo |
Sleep Disorder Opioid-use Disorder |
Massachusetts General Hospital | January 24, 2022 | Phase 2 Phase 3 |
| NCT05825235 | Recruiting | Drug: Pramipexole | Anhedonia Depression |
Region Skane | April 21, 2023 | Phase 3 |
| NCT05355337 | Recruiting | Drug: Pramipexole Drug: Placebo |
Anhedonia Depression |
Region Skane | February 8, 2023 | Phase 3 |
| NCT05748600 | Recruiting | Drug: Dexpramipexole Dihydrochloride Drug: Placebo |
Eosinophilic Asthma Asthma; Eosinophilic |
Areteia Therapeutics | January 30, 2023 | Phase 3 |
| NCT05003648 | Recruiting | Drug: Pramipexole Drug: Placebo |
Adrenoleukodystrophy Restless Legs Syndrome |
Massachusetts General Hospital | April 1, 2023 | Phase 4 |
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