| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
| Targets |
D2/D3 Receptor
Dopamine receptor stimulator/agonist. It is thought to act directly on postsynaptic dopamine receptors. [1] |
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| ln Vitro |
Piribedil (0-160 μM, 7 days) inhibits MLL1 methyltransferase activity in a particular manner and inhibits MLL-r cell growth in a targeted manner [4]. Piribedil (0-160 μM, 4 days) specifically inhibits the MLL1-WDR5 interaction, hence reducing H3K4 methylation in MLL-r cells (THP-1 and MV4; 11). MLL-r cells (THP-1 and MV4; 11) undergo cell cycle arrest, apoptosis, and differentiation when exposed to piribedil (0-160 μM) for four days [4].
No direct in vitro experiments on human cells or tissues were described in this clinical study. The paper references animal studies showing that piribedil decreases dopamine turnover and, in rats with caudate lesions, causes rotation toward the intact side of the brain in a dose-dependent manner. It also notes that the dopamine agonist effect of piribedil lasts two to three times longer than that of apomorphine in animal models. [1] |
| ln Vivo |
Piribedil (intraperitoneal injection, 5, 15, 40 mg/kg) reduces levodopa-induced dyskinesia in a rat model of Parkinson's disease [2]. Pirbedil (oral gavage, 4-5 mg/kg daily for 2 weeks) increases locomotor activity and reverses motor deficits in adult common marmosets [3]. Piribedil (150 mg/kg orally, daily for 21 days) inhibits MLL-r tumor growth and reduces MLL1 target gene expression in MV4;11 tumor xenografts [4].
In an initial nonblind study of 12 Parkinson's disease patients, oral administration of piribedil improved symptoms in 6 patients, with 4 patients showing improvement of 33% or more based on the Cornell Weighted Scale. The average improvement for all patients was 26%. [1] In a subsequent double-blind, placebo-controlled trial with 20 Parkinson's disease patients, 7 out of 18 patients who completed the study improved more than 25%, and 3 of these improved close to or more than 50% (49%, 64%, and 90%). The mean difference between placebo and piribedil scores was 44%, which was statistically significant at the 1% level. [1] Tremor was noted to improve more dramatically than other major symptoms of parkinsonism. Four of 6 patients with tremor as their major sign had a score change of more than 50% between placebo and piribedil trials, with an average change of 59% for these 6 patients. [1] Improvement with piribedil appeared to be related to the stage of Parkinson's disease. Both patients with stage I disease improved more than 50%, while 4 of 10 patients in stages II or III and none of 5 patients in stage IV showed similar improvement. [1] Eighteen patients completed the double-blind trial, and 8 of them continued taking piribedil with satisfactory results long-term. Three others stopped due to agitation or loss of therapeutic effect. [1] Piribedil was also given to 5 patients with essential tremor. Two had notable improvement in writing and hand use, but the other 3 were unchanged. It was not effective in one patient with progressive supranuclear palsy and another with Gilles de la Tourette's syndrome. [1] |
| Enzyme Assay |
Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA-approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non-MLL cells. Mechanism study showed Piribedil blocked the MLL1-WDR5 interaction and thus selectively reduced MLL1-dependent H3K4 methylation. Importantly, MLL1 depletion induced gene expression that was similar to that induced by Piribedil and rendered the MLL-r cells resistant to Piribedil-induced toxicity, revealing Piribedil exerted anti-leukemia effects by targeting MLL1. Furthermore, both the Piribedil treatment and MLL1 depletion sensitized the MLL-r cells to doxorubicin-induced apoptosis. Our study support the hypothesis that Piribedil could serve as a new drug for the treatment of MLL-r AML and provide new insight for further optimization of targeting MLL1 HMT activity.[4]
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| Cell Assay |
Cell proliferation assay[4]
Cell Types: MLL-r AML cells (THP-1 and MV4;11), non-MLL leukemia cell line (K562) Tested Concentrations: 0, 20, 40, 80 and 160 μM Incubation Duration: 0- 7 Experimental Results: Inhibited the growth rate of THP-1 and MV4;11 cells in a time-dependent manner. Western Blot Analysis[4] Cell Types: THP-1 and MV4; 11 cells Tested Concentrations: 0, 20, 40, 80 and 160 μM Incubation Duration: 4 days Experimental Results: H3K4me2 and H3K4me3 levels were diminished, but did not affect other histones Methylation, such as H3K79, H3K36 and H3K27. |
| Animal Protocol |
Animal/Disease Models: Parkinson's disease rat model [2]
Doses: 5, 15, 40 mg/kg Route of Administration: intraperitoneal (ip) injection, 5 minutes before levodopa administration. Experimental Results: Rotational behavior as well as AD (axial dystonia), OD (oral dyskinesia) and FD (forelimb dyskinesia) were diminished at doses of 5 and 40 mg/kg. LD (dyskinesia) increased at 40 mg/kg. Animal/Disease Models: Adult common marmoset [3] Doses: 4-5 mg/kg Route of Administration: po (oral gavage), one time/day for 2 weeks Experimental Results: Improved alertness and vigilance, reversed MPTP in rostral and caudal stripes Down-regulation of protachykinin mRNA induced in the cyst. The paper mentions animal studies (rats with caudate lesions, monkeys with tegmental lesions) conducted by other researchers (Corrodi et al., Goldstein et al.) that demonstrated piribedil's dopamine agonist effects, but no specific experimental protocols from these referenced studies are detailed in this paper. [1] The paper mentions animal studies (rats with caudate lesions, monkeys with tegmental lesions) conducted by other researchers (Corrodi et al., Goldstein et al.) that demonstrated piribedil's dopamine agonist effects, but no specific experimental protocols from these referenced studies are detailed in this paper. [1] |
| ADME/Pharmacokinetics |
The paper references work by Campbell, Jenner, and Taylor showing that piribedil is rapidly metabolized to an active metabolite, 1-(3,4-methylene dioxybenzyl)-4-(5-hydroxy-2-pyrimidinyl) piperazine (S 584), which is active on dopamine systems in animal models. [1]
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| Toxicity/Toxicokinetics |
Adverse effects of piribedil were similar to those of levodopa and included:
- Nausea (reported in 10 patients, limiting dose in 2) [1] - Dyskinesia (reported in 9 patients; all were taking levodopa with piribedil) [1] - Confusion or agitation (reported in 8 patients) [1] - Drowsiness (reported in 9 patients, more common with piribedil than levodopa) [1] - One patient experienced drug-related fever [1] - One patient with chronic pedal edema developed congestive heart failure with fluid retention and dyspnea, which resolved after stopping piribedil and initiating diuretic and cardiac therapy [1] - One 67-year-old woman became delirious and was found to have a malignant glioma (not attributed to drug) [1] - Laboratory tests remained normal except for a transient rise in alkaline phosphatase in one patient [1] A more gradual dosage schedule was suggested as a possible way to reduce adverse effects. [1] |
| References |
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| Additional Infomation |
2-[4-(1,3-benzodioxane-5-ylmethyl)-1-piperazinyl]pyrimidine is an N-arylpiperazine compound. Piribedil has been studied for Parkinson's disease. It is a dopamine D2 receptor agonist. It is used to treat Parkinson's disease, particularly to relieve tremors. It has also been used to treat circulatory disorders and other conditions, acting as a D2 receptor agonist.
Piribedil is a dopamine agonist that was investigated as a potential treatment for Parkinson's disease following the success of levodopa and the recognition that apomorphine (another dopamine agonist) had antiparkinsonian effects but was limited by side effects and azotemia with chronic oral use. [1] The study design included both nonblind and double-blind, placebo-controlled trials. Patients received oral coated 20-mg tablets of piribedil starting at 40 mg/day, increased by 20 mg every other day to a maximum of 300 mg/day, given in four divided doses after meals and at bedtime. In the double-blind study, patients received either drug or placebo for 4 weeks before crossing over. [1] Parkinsonian disability was scored using the Cornell Weighted Scale. Hematologic, renal, and hepatic function tests plus electrocardiograms were monitored in each patient. [1] The authors concluded that despite a high incidence of adverse effects making the drug difficult to use, piribedil's benefit in some patients demonstrates that dopamine receptor stimulators are potentially very helpful in treating Parkinson's disease. They suggested that the active metabolite (S 584) might be more effective clinically. [1] |
| Exact Mass |
298.142
|
|---|---|
| Elemental Analysis |
C, 64.41; H, 6.08; N, 18.78; O, 10.73
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| CAS # |
3605-01-4
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| Related CAS # |
Piribedil-d8;1398044-45-5;Piribedil dihydrochloride;1451048-94-4;Piribedil hydrochloride;78213-63-5
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| PubChem CID |
4850
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
469.4±55.0 °C at 760 mmHg
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| Melting Point |
98 °C
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| Flash Point |
237.7±31.5 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.632
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| LogP |
2.36
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
356
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCN1CC2=CC3=C(C=C2)OCO3)C4=NC=CC=N4
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| InChi Key |
OQDPVLVUJFGPGQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H18N4O2/c1-4-17-16(18-5-1)20-8-6-19(7-9-20)11-13-2-3-14-15(10-13)22-12-21-14/h1-5,10H,6-9,11-12H2
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| Chemical Name |
2-(4-Piperonyl-1-piperazinyl)pyrimidine
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| Synonyms |
Piribedil; EU 4200; EU-4200; ET-495 ET 495; ET495; ET495; EU4200
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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 |
| 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 : ~33.33 mg/mL (~111.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.38 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 (8.38 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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.
Link: https://clinicaltrials.gov/ct2/show/NCT01519856
Conditions:Parkinson's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT01007864
Conditions:Idiopathic Parkinson's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT00725478
Conditions:Parkinson's Disease
Title:SEDPARK2: Post Marketing Surveillance to Observe Safety and Efficacy of Piribedil in Parkinson's Disease (PIR-002/K)
Status:Completed
updateDate:2009-02-25
Ctid:NCT00727727
Link: https://clinicaltrials.gov/ct2/show/NCT00727727
Conditions:Parkinson's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT00591994
Conditions:TinnitusProducts are for research use only; We do not sell to patients
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