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Pramipexole 2HCl (also known as SND 919; (S)-Pramipexole HCl), an agonist of the Gαi-linked dopamine receptors D2, D3, and D4, is a potent dopamine agonist of the non-ergoline class that is used for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS). 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 |
D3 recepto ( Ki = 0.5 nM ); D2L Receptor ( Ki = 2.2 nM ); D2S Receptor ( Ki = 3.9 nM ); D4 receptor ( Ki = 5.1 nM )
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| ln Vitro |
Pramipexole dihydrochloride has a low binding affinity for D1-type receptors [1]. Pramipexole dihydrochloride (0.01-10 μM; 72 hours) increases soma cell size and dendritic structures proportionate to the dose. Pramipexole HCl reduces the toxicity caused by levodopa in cultures of the midbrain, suggesting that Pramipexole HCl may protect dopamine neurons in tissue culture [4].
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| ln Vivo |
Pramipexole hydrochloride (0.25-1 mg/kg; ip) considerably lowers the volume of the infarct in animals. Pramipexole hydrochloride enhances neurological healing. Through pathways, pramipexole hydrochloride prevents AIDS-induced cell death in stroke.
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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 |
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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| References |
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| Additional Infomation |
Pramipexole hydrochloride anhydrous is a hydrochloride that is the anhydrous dihydrochloride salt of pramipexole. It has a role as a dopamine agonist and an antiparkinson drug. It contains a pramipexole(2+).
Pramipexole Dihydrochloride is the hydrochloride salt of pramipexole, a benzothiazole derivative. As a nonergot dopamine agonist, pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra of the brain. Compared to other dopamine agonists, the use of this agent may be associated with fewer dyskinetic side effects in treated subjects. (NCI04) A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME. Sifrol is indicated for treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa, i. e. over the course of the disease, though to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end-of-dose or 'on-off' fluctuations). Sifrol is indicated for symptomatic treatment of moderate to severe idiopathic restless-legs syndrome in dosages up to 0. 54 mg of base (0. 75 mg of salt). |
| Molecular Formula |
C10H19CL2N3S
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|---|---|
| Molecular Weight |
284.25
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| Exact Mass |
283.07
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| Elemental Analysis |
C, 42.25; H, 6.74; Cl, 24.95; N, 14.78; S, 11.28
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| CAS # |
104632-25-9
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| Related CAS # |
Dexpramipexole dihydrochloride; 104632-27-1; Pramipexole; 104632-26-0; Pramipexole dihydrochloride hydrate; 191217-81-9; Dexpramipexole; 104632-28-2; Pramipexole-d7 dihydrochloride; Pramipexole-d5 dihydrochloride; 1217601-58-5; Pramipexole-d7-1 dihydrochloride; 2702798-58-9
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| PubChem CID |
119569
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| Appearance |
White to off-white solid powder
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| Boiling Point |
378ºC at 760 mmHg
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| Melting Point |
288-290ºC
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| Flash Point |
182.4ºC
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| Vapour Pressure |
6.49E-06mmHg at 25°C
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| LogP |
4.16
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| tPSA |
79.18
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| SMILES |
CCCN[C@H]1CCC2=C(C1)SC(=N2)N.Cl.Cl
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| InChi Key |
QMNWXHSYPXQFSK-KLXURFKVSA-N
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| InChi Code |
InChI=1S/C10H17N3S.2ClH/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8;;/h7,12H,2-6H2,1H3,(H2,11,13);2*1H/t7-;;/m0../s1
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| Chemical Name |
(6S)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dihydrochloride
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| Synonyms |
Pramipexole 2HCl; Pramipexole Dihydrochloride; Mirapex ER; Pramipexole hydrochloride; Pramipexole dihydrochloride; 104632-25-9; (S)-N6-Propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine dihydrochloride; Mirapex ER; PRAMIPEXOLE HYDROCHLORIDE; (S)-Pramipexole Dihydrochloride; PRAMIPEXOLE HCl; Pramipexole (dihydrochloride); SND919; Mirapex; SUD 919CL2Y; SUD919CL2Y; U-98528E; Sifrol; SND 919; KNS-760704
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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 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)
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| Solubility (In Vitro) |
DMSO: ~56 mg/mL (~197.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (351.80 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5180 mL | 17.5901 mL | 35.1803 mL | |
| 5 mM | 0.7036 mL | 3.5180 mL | 7.0361 mL | |
| 10 mM | 0.3518 mL | 1.7590 mL | 3.5180 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.
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