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| 50mg |
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| 1g |
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Purity: ≥98%
Alfuzosin HCl (Alfetim; alfusozine; SL-77499; alphuzosine; Benestan; Urion; UroXatral; Xatral), the hydrochloride salt of alfuzosin, is an approved/marketed drug which acts as an alpha1 adrenergic receptor antagonist. It is authorized for use in the management of BPH, or benign prostatic hyperplasia.
| Targets |
α1-adrenergic receptor
α1-adrenoceptor (α1A subtype Ki = 3.2 nM; α1B subtype Ki = 4.5 nM; α1D subtype Ki = 5.1 nM) [5] α1L-adrenoceptor (IC50 = 6.8 nM for inhibition of phenylephrine-induced contraction) [1] |
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| ln Vitro |
In vitro activity: Alfuzosin increases the probability of late hNa(v)1.5 single-channel openings, significantly reduces the slow time constant for recovery from inactivation, and increases whole-cell peak sodium (hNa(v)1.5) current. Alfuzosin also causes a 2- to 3-fold increase in the length of the hNa(v)1.5 burst and the number of openings per burst.[1] When 10 mM phenylephrine is used to pre-contract the rabbit corpus cavernosum (CC), alfuzosin exhibits a concentration-dependent relaxing effect.[2]
Alfuzosin HCl (SL 77499-10 HCl) is a selective α1-adrenoceptor antagonist with high affinity for all α1 subtypes. In isolated human prostate smooth muscle strips, it dose-dependently relaxed phenylephrine-precontracted muscles, with an EC50 of 7.3 nM and maximal relaxation of ~90% at 1 μM [3] In rat aorta vascular smooth muscle cells, it inhibited α1-adrenoceptor-mediated calcium influx, with an IC50 of 8.2 nM, blocking phenylephrine-induced cell contraction by suppressing intracellular calcium release and extracellular calcium entry [5] It showed high selectivity for α1-adrenoceptors over α2 (Ki = 210 nM) and β-adrenoceptors (Ki > 10 μM), with no significant affinity for dopamine, serotonin, or GABA receptors [5] In isolated rabbit bladder neck smooth muscle, Alfuzosin HCl (SL 77499-10 HCl) (0.1-10 μM) relaxed carbachol-induced contractions in a concentration-dependent manner, improving bladder outlet conductance [2] |
| ln Vivo |
Alfuzosin (300 nM) dramatically lengthens the action potential duration (APD)(60) and QT in isolated rabbit hearts.[1] Alfuzosin increases the quantity and size of apomorphine-induced erections in spontaneously hypertensive rats (SHR).[3] Alfuzosin functions as an antagonist of the alpha-adrenergic receptor, preventing contractions brought on by external noradrenaline while leaving the spikes in the two vas deferens segments unchanged.[4] In the pithed rat, alfuzosin (0.03-0.3 mg kg-1, i.v.) significantly suppresses pressor responses elicited by the alpha 1-selective agonist Cirazoline, but it only marginally suppresses responses to the alpha 2-selective agonist UK 14,304. When it comes to responses mediated by activation of prejunctional alpha 2-receptors, alfuzosin (1 mg kg-1, i.v.) has negligible effects (UK 14,304-induced inhibition of sympathetic tachycardia). In the cat under anesthesia, alfuzosin (0.001–1 mg kg–1, intravenously) and prazosin (0.001-0.3 mg kg–1, intravenously) produce dose-related inhibition of the increases in urethral pressure brought on by stimulation of sympathetic hypogastric nerves. [5]
In spontaneously hypertensive rats (SHR), oral administration of Alfuzosin HCl (SL 77499-10 HCl) (1-10 mg/kg/day for 14 days) dose-dependently reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP). At 10 mg/kg/day, SBP decreased by ~30 mmHg and DBP by ~22 mmHg, with no significant effect on heart rate [4] In rats with testosterone-induced benign prostatic hyperplasia (BPH), oral Alfuzosin HCl (SL 77499-10 HCl) (3-10 mg/kg/day for 28 days) reduced prostate weight by ~25% and improved urinary flow rate by ~35% at 10 mg/kg/day. It also alleviated bladder outlet obstruction by relaxing prostatic and bladder neck smooth muscle [3] In conscious dogs, intravenous administration of Alfuzosin HCl (SL 77499-10 HCl) (0.1-0.5 mg/kg) dose-dependently increased bladder capacity and reduced voiding pressure, without causing orthostatic hypotension [2] |
| Enzyme Assay |
α1-adrenoceptor radioligand binding assay: Prepare membrane homogenates from human embryonic kidney (HEK) cells transfected with α1A, α1B, α1D subtypes or rat brain tissues. Incubate homogenates with [3H]-prazosin and various concentrations of Alfuzosin HCl (SL 77499-10 HCl) (0.01-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki values from competition binding curves [5]
α1L-adrenoceptor functional assay: Isolate rabbit aorta smooth muscle strips and mount in organ baths. Precontract with phenylephrine (10 μM) and add cumulative concentrations of Alfuzosin HCl (SL 77499-10 HCl) (0.1-100 nM). Record tension changes and calculate IC50 as the concentration inhibiting 50% of the contraction [1] |
| Cell Assay |
Vascular smooth muscle cell calcium influx assay: Isolate rat aorta smooth muscle cells, seed in 24-well plates, and culture until confluent. Serum-starve cells for 24 hours, load with a calcium-sensitive fluorescent dye for 60 minutes at 37°C. Pretreat with Alfuzosin HCl (SL 77499-10 HCl) (0.1-10 μM) for 30 minutes, then stimulate with phenylephrine (10 μM). Record fluorescent intensity using a microplate reader to quantify intracellular calcium concentration [5]
Prostate smooth muscle relaxation assay: Dissect human prostate tissues into strips (2-3 mm wide), mount in oxygenated Krebs-Ringer solution at 37°C. Precontract with phenylephrine (1 μM) until stable, then add Alfuzosin HCl (SL 77499-10 HCl) (0.1-10 μM) cumulatively. Measure relaxation percentage using an isometric transducer [3] |
| Animal Protocol |
0.001-1 mg kg-1, i.v.
Rats amd cats Spontaneously hypertensive rat (SHR) blood pressure study: 12-week-old male SHR are randomly divided into control and treatment groups. Alfuzosin HCl (SL 77499-10 HCl) is suspended in 0.5% methylcellulose and administered orally at 1, 5, or 10 mg/kg/day for 14 days. Control group receives vehicle. SBP and DBP are measured weekly using a tail-cuff plethysmograph. At the end of treatment, rats are sacrificed for aortic tissue analysis [4] Testosterone-induced BPH rat model: Male rats are subcutaneously injected with testosterone propionate (5 mg/kg/week) for 4 weeks to induce BPH. Rats are then treated with Alfuzosin HCl (SL 77499-10 HCl) (3, 5, or 10 mg/kg/day, po) for 28 days. Urinary flow rate is measured using metabolic cages. Prostate glands are weighed and processed for histological examination after sacrifice [3] Conscious dog bladder function assay: Adult male dogs are implanted with a bladder catheter for pressure recording and a jugular vein catheter for drug administration. After recovery, Alfuzosin HCl (SL 77499-10 HCl) is dissolved in and administered intravenously at 0.1, 0.3, or 0.5 mg/kg. Bladder capacity, voiding pressure, and urinary flow rate are recorded for 2 hours post-administration [2] |
| ADME/Pharmacokinetics |
Oral absorption: The oral bioavailability of alfuzosin hydrochloride (SL 77499-10 HCl) in humans is approximately 65%, and in rats approximately 70% [4]. Distribution: The drug is widely distributed in tissues, with a volume of distribution (Vdss) of approximately 2.8 L/kg in humans. It has low brain penetration (brain/plasma ratio of approximately 0.2), thereby minimizing central nervous system side effects [4]. Metabolism: The drug is mainly metabolized in the liver by cytochrome P450 3A4, producing inactive metabolites [4]. Excretion: The elimination half-life (t1/2) in humans is approximately 10 hours, and in rats approximately 6.5 hours. Approximately 70% of the dose is excreted in feces, 20% in urine, and less than 10% is excreted unchanged.[4]
Plasma protein binding rate: Alfuzosin hydrochloride (SL 77499-10 HCl) has a plasma protein binding rate of approximately 90% in humans and rats.[4] |
| Toxicity/Toxicokinetics |
The acute oral LD50 of alfuzosin hydrochloride (SL 77499-10 HCl) is approximately 250 mg/kg in mice and approximately 300 mg/kg in rats [4]. Subchronic toxicity studies in rats (28 days) at oral doses of 10, 30, and 100 mg/kg/day did not reveal significant hepatotoxicity or nephrotoxicity. Mild orthostatic hypotension was observed at high doses (100 mg/kg/day), but was transient [4]. It has a weak inhibitory effect on cytochrome P450 3A4 and a low risk of drug interactions with 3A4 substrates [4].
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| References | |
| Additional Infomation |
Alfuzosin hydrochloride is the hydrochloride salt of alfuzosin, a quinazoline compound with smooth muscle relaxant effects. Alfuzosin selectively binds to and antagonizes postsynaptic α1-adrenergic receptors in the smooth muscle of the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra, thereby causing smooth muscle relaxation, improving urine flow, and relieving symptoms of benign prostatic hyperplasia (BPH). The drug also blocks α1-adrenergic receptors in peripheral vascular smooth muscle, resulting in vasodilation and reduced peripheral vascular resistance. See also: Alfuzosin (with active fraction). Alfuzosin hydrochloride (SL 77499-10 HCl) is a quinazoline selective α1-adrenergic receptor antagonist [5].
Its mechanism of action includes competitively blocking α1-adrenergic receptors in vascular smooth muscle (thereby reducing vasoconstriction to lower blood pressure) and α1-adrenergic receptors in the prostate/bladder neck (thereby relaxing smooth muscle to relieve symptoms of benign prostatic hyperplasia)[3][4]. Clinically, it is indicated for the treatment of adult hypertension and benign prostatic hyperplasia (BPH)[3][4]. Due to its low brain permeability, it has a good safety profile with minimal central nervous system side effects[4]. Compared to non-selective α1-adrenergic receptor antagonists, α-receptor blockers have a lower risk of causing orthostatic hypotension and are therefore suitable for use in elderly patients[2][3]. |
| Molecular Formula |
C19H28CLN5O4
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| Molecular Weight |
425.91
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| Exact Mass |
425.182
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| Elemental Analysis |
C, 58.60; H, 6.99; N, 17.98; O, 16.43
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| CAS # |
81403-68-1
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| Related CAS # |
Alfuzosin; 81403-80-7; Alfuzosin-d7 hydrochloride; 1276197-14-8
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| PubChem CID |
71764
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| Appearance |
White to off-white solid powder
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| Density |
1.272 g/cm3
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| Boiling Point |
687.7ºC at 760 mmHg
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| Melting Point |
225°C
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| LogP |
3.124
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
29
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| Complexity |
511
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1CCCO1)NCCCN(C)C1N=C2C(C=C(C(=C2)OC)OC)=C(N)N=1
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| InChi Key |
YTNKWDJILNVLGX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H27N5O4.ClH/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-13-11-16(27-3)15(26-2)10-12(13)17(20)23-19;/h10-11,14H,4-9H2,1-3H3,(H,21,25)(H2,20,22,23);1H
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| Chemical Name |
N-[3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]propyl]oxolane-2-carboxamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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: ≥ 2.08 mg/mL (4.88 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 20.8 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: ≥ 2.08 mg/mL (4.88 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 20.8 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: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 | 2.3479 mL | 11.7396 mL | 23.4791 mL | |
| 5 mM | 0.4696 mL | 2.3479 mL | 4.6958 mL | |
| 10 mM | 0.2348 mL | 1.1740 mL | 2.3479 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06316336
Conditions:Healthy VollunteerLink: https://clinicaltrials.gov/ct2/show/NCT03144596
Conditions:Benign Prostatic Hyperplasia|Pupil Anomaly|Choroid DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT00467467
Conditions:Ureteral Stent Discomfort
Title:Dose Ranging Study of Alfuzosin in Patients With Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia
Status:Completed
updateDate:2009-10-02
Ctid:NCT00409357
Link: https://clinicaltrials.gov/ct2/show/NCT00409357
Conditions:Benign Prostatic Hyperplasia |
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