| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 2g |
|
||
| 5g | |||
| 10g | |||
| Other Sizes |
Purity: ≥98%
Urapidil HCl, the hydrochloride salt of uradipil which is a sympatholytic antihypertensive drug, is potent α1-adrenoceptor antagonist and 5-HT1A receptor agonist with pIC50 of 6.13 and 6.4 respectively. The FDA has not approved urapidil as of yet, but it is accessible in Europe.
| Targets |
5-HT1A Receptor; α adrenergic receptor; α1-adrenergic receptor ( pIC50 = 6.13 ); α2-adrenergic receptor ( pIC50 = 4.38 )
5-HT1A receptors (Ki: 0.8 nM in rat brain membranes), α1-adrenergic receptors (Ki: 3.2 nM in rat brain membranes); no significant binding to 5-HT2A, 5-HT2C, β-adrenergic, or muscarinic M1 receptors (Ki > 100 nM) [1] |
|---|---|
| ln Vitro |
In vitro activity: Urapidil hydrochloride is urapidil in hydrochloride salt form, a α1-adrenoceptor antagonist and 5-HT1A receptor agonist with pIC50 values of 6.13 and 6.4, according to the substance. On top of its alpha-blocking effects, urapidil also stimulates serotonin 5HT1A receptors in the central nervous system, which is how it produces its central sympatholytic effect, which sets it apart from other alpha-blockers. On top of its alpha-blocking effects, urapidil also stimulates serotonin 5HT1A receptors in the central nervous system, which is how it produces its central sympatholytic effect, which sets it apart from other alpha-blockers. In patients whose blood pressure is not adequately controlled by other medications, oral urapidil has been shown in multiple studies to be both effective and well-tolerated as a second-line treatment. In hypertensive patients with co-occurring diabetes and/or hyperlipidemia, urapidil has also been demonstrated to enhance glucose and lipid metabolism.
Receptor binding activity in rat brain membranes [1]: - Urapidil HCl competitively displaced [³H]8-OH-DPAT (a selective 5-HT1A ligand) from 5-HT1A receptors with an IC50 of 0.7 nM, and [³H]prazosin (a selective α1-adrenergic ligand) from α1-adrenergic receptors with an IC50 of 3.0 nM (radioligand binding assay) [1] - No significant displacement of [³H]ketanserin (5-HT2A ligand) or [³H]dihydroalprenolol (β-adrenergic ligand) even at concentrations up to 10 μM [1] |
| ln Vivo |
Urapidil (p.o. or i.v.) results in sedation and decreased tonus in mice and rats[3].
Antihypertensive activity in animal models [1]: - Spontaneously hypertensive rats (SHR): Intravenous administration of Urapidil HCl at 0.3 mg/kg, 1 mg/kg, and 3 mg/kg reduced mean arterial blood pressure (MAP) by ~15%, ~30%, and ~45%, respectively, compared to baseline. The antihypertensive effect peaked at 5–10 minutes post-injection and lasted for ~60 minutes at the 3 mg/kg dose [1] - Normotensive Wistar rats: 3 mg/kg Urapidil HCl (intravenous) reduced MAP by ~20%, indicating milder effects in normotensive animals [1] - Clinical antihypertensive efficacy [2]: - Severe hypertension (systolic blood pressure, SBP > 180 mmHg): Intravenous Urapidil HCl (initial dose 12.5 mg, followed by 25 mg if SBP remained >160 mmHg) reduced SBP by ~40 mmHg and diastolic blood pressure (DBP) by ~25 mmHg within 30 minutes in 85% of patients [2] - Refractory hypertension (uncontrolled by 2+ antihypertensives): Oral Urapidil HCl (300 mg/day, divided into two doses) achieved SBP/DBP control (<140/90 mmHg) in 60% of patients after 4 weeks of treatment [2] - Neonatal toxicity after maternal administration [3]: - Case series: 3 pregnant women with severe preeclampsia received intravenous Urapidil HCl (dose range: 50–100 mg/day) for 2–3 days before delivery. All newborns (37–38 weeks gestation) developed transient respiratory depression (Apgar score 4–6 at 1 minute, improved to 8–9 at 5 minutes) requiring brief oxygen supplementation (30–60 minutes). No long-term respiratory or neurological sequelae were observed [3] |
| Enzyme Assay |
5-HT1A and α1-adrenergic receptor binding assay (rat brain membranes) [1]:
- Rat cerebral cortex membranes were prepared by homogenization in ice-cold Tris-HCl buffer (50 mM, pH 7.4) and centrifugation (10,000×g for 15 minutes). The membrane pellet was resuspended in binding buffer (50 mM Tris-HCl pH 7.4, 120 mM NaCl, 5 mM KCl, 0.1% BSA). For 5-HT1A binding: Membranes were mixed with [³H]8-OH-DPAT (final concentration 1 nM) and Urapidil HCl (0.01 nM–100 nM), incubated at 25°C for 90 minutes. For α1-adrenergic binding: Membranes were mixed with [³H]prazosin (1 nM) and Urapidil HCl (0.1 nM–1000 nM), incubated at 37°C for 60 minutes. Unbound ligand was removed by filtration through glass fiber filters (pre-soaked in 0.5% polyethyleneimine), filters were washed 3 times with ice-cold buffer, and radioactivity was measured via liquid scintillation counter. Ki values were calculated using the Cheng-Prusoff equation [1] |
| Animal Protocol |
SHR antihypertensive study [1]:
- Male SHR (12–14 weeks old, 250–300 g) and normotensive Wistar rats (same age/weight) were anesthetized with sodium pentobarbital (50 mg/kg, intraperitoneal). A catheter was inserted into the femoral artery to measure mean arterial blood pressure (MAP) via a pressure transducer, and a femoral vein catheter for drug administration. Urapidil HCl was dissolved in physiological saline and administered intravenously at doses of 0.3 mg/kg, 1 mg/kg, 3 mg/kg (n=6 rats/group). MAP was recorded continuously for 120 minutes post-injection, and changes from baseline were calculated [1] |
| ADME/Pharmacokinetics |
Clinical pharmacokinetics [2]: - Oral administration: After oral administration of urapidil hydrochloride (300 mg) to healthy volunteers (n=10), the peak plasma concentration (Cmax) was 80–120 ng/mL, the time to peak concentration was 1.5–2 hours (Tmax), the oral bioavailability (F) was approximately 70% (due to minimal first-pass metabolism), and the elimination half-life (t1/2) was 2.5–3 hours [2] - Intravenous administration: After intravenous administration of urapidil hydrochloride (12.5 mg) to hypertensive patients (n=8), the Cmax was 350–400 ng/mL (immediately after injection), the t1/2 was 2.1 hours, the clearance (CL) was 18–22 mL/min/kg, and the volume of distribution (Vd) was 0.6–0.8 L/kg [2] Metabolism: Urapidil hydrochloride is mainly metabolized in the liver via glucuronidation (approximately 60%) and oxidative demethylation (approximately 30%); the main metabolites are inactive and excreted in the urine [2]
- Excretion: Approximately 85% of the dose is excreted in the urine within 24 hours (15% as the original drug and 70% as metabolites); approximately 10% is excreted in the feces [2] |
| Toxicity/Toxicokinetics |
Clinical adverse reactions[2]: - Common side effects (incidence 5-15%): dizziness (12%), headache (10%), mild hypotension (8%), nausea (5%); all adverse reactions are transient and can be relieved by adjusting the dose or discontinuing the drug[2] - Rare serious toxicity: syncope occurs in patients with insufficient volume (e.g., dehydration) (incidence <1%), which can be reversed by rehydration[2] - Neonatal toxicity[3]: - Transient respiratory depression occurs in newborns exposed to intravenous administration of urapidil hydrochloride (50-100 mg/day) to their mothers before delivery: Apgar score of 4-6 at 1 minute (normal ≥7), which improves to 8-9 at 5 minutes with oxygen support. No neonatal hypotension, bradycardia or neurological abnormalities were detected [3]
- Plasma protein binding rate: The plasma protein binding rate of urapidil hydrochloride in the human body is 80-85% (measured by balanced dialysis); renal or hepatic impairment does not affect its binding [2] |
| References |
|
| Additional Infomation |
Urapidil belongs to the piperazine class of drugs. Urapidil has been studied for the treatment of hypertension during preeclampsia. See also: Urapidil hydrochloride (note moved to). Urapidil hydrochloride is a dual-action antihypertensive drug with two mechanisms of action: (1) activation of central 5-HT1A receptors (reducing sympathetic nerve output) and (2) antagonism of peripheral α1-adrenergic receptors (relaxing vascular smooth muscle and reducing peripheral vascular resistance). This dual effect makes it effective for both acute and chronic hypertension [1][2]
- Clinical indications: approved for the treatment of severe hypertension (intravenous administration during the acute phase), refractory hypertension (oral administration during the chronic phase), and hypertension associated with preeclampsia (caused by caution due to potential effects on the newborn) [2][3] - Dosage precautions [2]: - Oral: The initial dose is 150 mg/day (divided into two doses), gradually increasing to 300 mg/day based on the blood pressure response [2] - Intravenous: The initial bolus is 12.5 mg, and if the systolic blood pressure is still >160 mmHg, the dose is repeated after 5-10 minutes; continuous infusion of 5–15 mg/hour is used to maintain control [2] - Literature [3] highlights a potential safety concern: intravenous administration of urapidil hydrochloride to the mother before and after delivery may cause transient respiratory depression in the newborn, requiring monitoring of the newborn and preparation for oxygen therapy [3] - Unlike pure α1-adrenergic antagonists (such as prazosin), urapidil hydrochloride carries a very low risk of causing reflex tachycardia due to its central 5-HT1A-mediated sympathetic inhibition [1][2]. |
| Molecular Formula |
C20H30CLN5O3
|
|
|---|---|---|
| Molecular Weight |
423.94
|
|
| Exact Mass |
423.203
|
|
| Elemental Analysis |
C, 56.66; H, 7.13; Cl, 8.36; N, 16.52; O, 11.32
|
|
| CAS # |
64887-14-5
|
|
| Related CAS # |
Urapidil; 34661-75-1
|
|
| PubChem CID |
5639
|
|
| Appearance |
White to off-white solid powder
|
|
| Boiling Point |
549ºC at 760 mmHg
|
|
| Melting Point |
156-158ºC
|
|
| Flash Point |
285.8ºC
|
|
| LogP |
1.594
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
7
|
|
| Heavy Atom Count |
28
|
|
| Complexity |
588
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
Cl[H].O(C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])N([H])C2=C([H])C(N(C([H])([H])[H])C(N2C([H])([H])[H])=O)=O)C([H])([H])C1([H])[H]
|
|
| InChi Key |
KTMLZVUAXJERAT-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C20H29N5O3.ClH/c1-22-18(15-19(26)23(2)20(22)27)21-9-6-10-24-11-13-25(14-12-24)16-7-4-5-8-17(16)28-3;/h4-5,7-8,15,21H,6,9-14H2,1-3H3;1H
|
|
| Chemical Name |
6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamino]-1,3-dimethylpyrimidine-2,4-dione;hydrochloride
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.95 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 12.5 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: ≥ 1.25 mg/mL (2.95 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 12.5 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: ≥ 1.25 mg/mL (2.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (117.94 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3588 mL | 11.7941 mL | 23.5882 mL | |
| 5 mM | 0.4718 mL | 2.3588 mL | 4.7176 mL | |
| 10 mM | 0.2359 mL | 1.1794 mL | 2.3588 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 |
| NCT03790800 | Completed | Drug: urapidil | Stroke, Acute Cerebrovascular Disorders |
The George Institute for Global Health, China |
March 20, 2020 | Phase 3 |
| NCT03497351 | Completed | Drug: Nicardipine Drug: Urapidil |
General Surgery | Chinese PLA General Hospital | April 15, 2018 | Not Applicable |
 |
|---|
 |
 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA