Alfuzosin is a selective and competitive antagonist of the α1-adrenergic receptor. It exhibits high selectivity for α1 receptors and does not significantly affect β1, β2, H1, H2, or muscarinic receptors. Its primary site of action is the α1-adrenoceptors located in the smooth muscle of the prostate, bladder neck, and urethra. By blocking these receptors, Alfuzosin inhibits the action of norepinephrine, a neurotransmitter that causes smooth muscle contraction. This results in relaxation of the prostate and bladder neck muscles, alleviating the obstruction and improving urinary flow in patients with BPH. Its moderate protein binding (82-90%) contributes to its pharmacokinetic profile.

In vitro, Alfuzosin acts as a competitive antagonist at α1-adrenoceptors. It has been shown to relax isolated prostate and urethral smooth muscle preparations by blocking norepinephrine-induced contractions. Its selectivity for α1-adrenoceptors over other receptor types (β1, β2, H1, H2, muscarinic) has been confirmed in receptor binding and functional assays. Alfuzosin's binding to human serum albumin is 68.2% and to human serum α1-glycoprotein is 52.5%. The compound has a moderate protein binding ranging from 82% to 90%.

Alfuzosin hydrochloride (10 mg/kg, oral; single dosage) blocks the effects of phenylephrine on urethral and arterial pressure rises in less than six hours [1].
In vivo, Alfuzosin is effective in reducing the symptoms of benign prostatic hyperplasia (BPH). It relaxes the muscles of the prostate and bladder neck, aiding in urination. It is administered orally and is well-absorbed. Its antihypertensive effects are not due to vagal reflexes and are not dependent on endogenous vasodilatory substances like prostaglandins. It is used clinically to improve urine flow and reduce the discomfort associated with LUTS. Alfuzosin is also used in research on lower urinary tract symptoms and ejaculatory dysfunction (EjD).

For in vitro cell-free assays, the binding affinity of Alfuzosin to α1-adrenoceptors can be measured using radioligand binding assays. In these assays, membrane preparations from tissues expressing α1-adrenoceptors (e.g., rat prostate or transfected cells) are incubated with a radiolabeled ligand specific for the α1 receptor, such as [3H]prazosin, in the presence of varying concentrations of Alfuzosin. The amount of bound radioligand is measured, and the Ki value, which represents the binding affinity of Alfuzosin, is calculated from a competition binding curve. The selectivity of Alfuzosin for α1 over other receptor subtypes can be confirmed by performing similar assays using membranes expressing β1, β2, H1, H2, or muscarinic receptors.

For cellular assays, the functional antagonism of Alfuzosin at α1-adrenoceptors can be assessed in cells expressing the receptor, such as smooth muscle cells or heterologous expression systems. Cells are loaded with a calcium-sensitive fluorescent dye, and the increase in intracellular calcium induced by an α1 agonist (e.g., phenylephrine) is measured using a fluorometric imaging plate reader (FLIPR). Alfuzosin is added to the cells prior to agonist stimulation, and the reduction in the calcium signal, indicating receptor blockade, is measured. The IC50 or pA2 value, which represents the potency of the antagonist, is calculated from the concentration-response curves.

Animal/Disease Models: Male Wistar rat (250-450 g) [1].
Doses: 10 mg/kg
Route of Administration: Oral; single.
Experimental Results: Prostate concentrations increased to 4.1-8.6 times the plasma concentration.
For in vivo studies, animal models of BPH, such as rats with testosterone-induced prostatic hyperplasia, are commonly used to evaluate the efficacy of Alfuzosin. The compound is administered orally or intravenously, and its effect on intraurethral pressure or urine flow rate is measured. Its cardiovascular effects are assessed by monitoring blood pressure and heart rate in normotensive or hypertensive animal models. Its selectivity for the prostate over vascular smooth muscle can be evaluated by comparing the doses required to relax the prostate versus those that cause a significant drop in blood pressure.

Absorption, Distribution and Excretion
Alfuzosin is readily absorbed in the gastrointestinal tract, with an absolute bioavailability of 49% after food intake. Absorption is faster and peak plasma concentrations are higher in patients over 75 years of age. Some data indicate a bioavailability of up to 64%. After multiple doses in the food-ingested state, peak plasma concentration (Cmax) is reached within 8 hours. Cmax and AUC0-24 values are approximately 13.6 ng/mL and 194 ng·h/mL, respectively. Steady-state plasma concentrations are reached after the second dose, which are 1.2 to 1.6 times higher than after a single dose. Sustained-release formulations allow for sustained release of alfuzosin for 20 hours, with dissolution rates ranging from 2 to 12 hours. Alfuzosin is partially metabolized and primarily excreted via bile and feces. One week after oral administration of radiolabeled alfuzosin solution, the detection rate of radioactive substances in feces was 69%, and in urine, it was 24%.
The volume of distribution of alfuzosin after intravenous injection in healthy volunteers is approximately 3.2 L/kg. Alfuzosin is mainly distributed in prostate tissue.
Caution should be exercised when renal clearance is <30 mL/min. In renal insufficiency (whether or not dialysis is performed), the clearance of alfuzosin will also increase due to the increased proportion of free drug.
After oral administration of (14)C-labeled alfuzosin solution, the recovery rate of radioactive material in feces after 7 days was 69% (as a percentage of the administered dose) and 24% in urine. Alfuzosin hydrochloride
The volume of distribution of alfuzosin after intravenous injection in healthy middle-aged male volunteers is 3.2 L/kg. In vitro studies have shown that alfuzosin has a moderate binding rate to human plasma proteins (82% to 90%) and linear binding over a wide concentration range (5 to 5000 ng/mL). The absorption rate of alfuzosin hydrochloride is reduced by 50% in the fasting state. Therefore, Uroxatral should be taken immediately after a meal. The absolute bioavailability of 10 mg Uroxatral tablets of alfuzosin hydrochloride in a postprandial state is 49%. The time to peak concentration is 8 hours after multiple 10 mg doses of Uroxatral. The Cmax and AUC0-24 of Uroxatral are 13.6 (SD = 5.6) ng/mL and 194 (SD = 75) ng·h/mL, respectively. Uroxatral exhibits linear pharmacokinetics after both single and multiple doses (up to 30 mg). Steady-state plasma concentrations are reached after the second dose of Uroxatral. Steady-state plasma concentrations of alfuzosin are 1.2 to 1.6 times higher than those observed after a single dose. /Sustained-Release Alfuzosin Hydrochloride/
For more complete data on absorption, distribution, and excretion of alfuzosin (6 items), please visit the HSDB record page.

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Metabolism/Metabolites
Alfuzosin is primarily metabolized in the liver; only 11% of the administered dose is detected unchanged in the urine. Alfuzosin is metabolized via three pathways: oxidation, O-demethylation, and N-dealkylation. The metabolites of alfuzosin are pharmacologically inactive, and CYP3A4 is the major hepatic cytochrome enzyme responsible for its metabolism.
Alfuzosin is extensively metabolized in the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized via three pathways: oxidation, O-demethylation, and N-dealkylation. The metabolites are pharmacologically inactive. CYP3A4 is the major hepatic isoenzyme involved in its metabolism. /Alfuzosin Hydrochloride/

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Biological Half-Life
The apparent elimination half-life of oral alfuzosin is approximately 10 hours. The terminal half-life is 3–5 hours.
The apparent elimination half-life after oral administration of 10 mg eulotoxam tablets is 10 hours. /Sustained-release alfuzosin hydrochloride/
Alfuzosin has a molecular formula of C19H27N5O4 and a molecular weight of 389.45 g/mol. It is typically supplied as a powder. For in vitro studies, it is dissolved in DMSO to prepare stock solutions (e.g., 10 mM in DMSO). For in vivo administration, it can be formulated in suitable vehicles. Recommended storage conditions for the powder are -20°C for 3 years or 4°C for 2 years. Its protein binding is moderate, ranging from 82% to 90%, with binding to human serum albumin at 68.2% and to α1-glycoprotein at 52.5%.

Hepatotoxicity
Alfuzosin was associated with a low incidence of elevated serum transaminases (probability score: C (likely to cause clinically significant liver injury)).

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Protein Binding
Alfuzosin has moderate protein binding, ranging from 82% to 90%. It binds to human serum albumin at 68.2% and to human serum α1-glycoprotein at 52.5%.

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Interactions
In 8 healthy young male volunteers, a single dose of 100 mg atenolol and a single dose of 2.5 mg immediate-release alfuzosin tablets increased the Cmax and AUC values of alfuzosin by 28% and 21%, respectively. Alfuzosin increased the Cmax and AUC values of atenolol by 26% and 14%, respectively. In this study, the combination of alfuzosin and atenolol significantly reduced mean blood pressure and mean heart rate.
Repeated daily administration of 1 gram of cimetidine increased the Cmax and AUC values of alfuzosin by 20%.
Repeated daily administration of 240 mg diltiazem (a moderate-potency CYP3A4 inhibitor) in combination with 7.5 mg/day (2.5 mg three times daily) of alfuzosin increased the Cmax and AUC0-24 of alfuzosin by 1.5-fold and 1.3-fold, respectively. Alfuzosin increased the Cmax and AUC0-12 of diltiazem by 1.4-fold. Although no changes in blood pressure were observed in this study, diltiazem is an antihypertensive drug, and the combination of euoxatol with antihypertensive drugs may cause hypotension in some patients. Alfuzosin hydrochloride
After repeated administration of 400 mg ketoconazole (a potent CYP3A4 inhibitor), a single dose of 10 mg alfuzosin increased the Cmax of alfuzosin by 2.3-fold and the AUClast by 3.2-fold. Euloxacillin should not be used concomitantly with potent CYP3A4 inhibitors (such as ketoconazole, itraconazole, or ritonavir). Alfuzosin Hydrochloride
For more complete data on drug interactions of alfuzosin (9 in total), please visit the HSDB record page.
Alfuzosin has a well-established clinical safety profile. Common side effects include dizziness, headache, and asthenia. Postural hypotension and syncope are less common than with non-selective α1-blockers. It is generally well-tolerated. No specific preclinical toxicity data is detailed in the provided sources, but as an approved drug, it has undergone extensive toxicological evaluation. Its safety in patients with hepatic or renal impairment has been established through clinical studies.

[1]. Relationship between the effects of alfuzosin on rat urethral and blood pressures and its tissue concentrations. Life Sci. 1998;63(3):169-76.

[2]. Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs. 1993 Mar;45(3):410-29.

Alfuzosin is a monocarboxylic acid amide, tetrahydrofuranol compound, belonging to the quinazoline class. It possesses pharmacological effects including antitumor, antihypertensive, and alpha-adrenergic antagonist activity. Benign prostatic hyperplasia (BPH) refers to benign enlargement of the prostate gland, leading to lower urinary tract symptoms in men, such as urinary urgency, frequency, and changes in urine flow. The prevalence of BPH in men over 60 years of age is as high as 50%-60%, and in men over 70 years of age, it reaches 80%-90%. Alfuzosin is an alpha-1 adrenergic blocker used for the symptomatic treatment of BPH. Its mechanism of action is through relaxation of the muscles of the prostate and bladder neck. Alfuzosin was initially approved by the U.S. Food and Drug Administration (FDA) in 2003 and is marketed by several pharmaceutical companies. Alfuzosin is an alpha-adrenergic blocker. Its mechanism of action is as an alpha-adrenergic receptor antagonist. Alfuzosin is a non-selective α-1-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). Transient elevations of serum transaminases caused by alfuzosin are rare, and clinically significant acute liver injury is uncommon. Alfuzosin is a synthetic quinazoline compound with smooth muscle relaxant effects. It selectively binds to and antagonizes α-1-adrenergic receptors in the smooth muscle of the bladder neck and prostate, thereby relaxing the smooth muscle and reducing obstruction and urethral resistance caused by BPH and prostate cancer. The drug also blocks α1-adrenergic receptors in the smooth muscle of peripheral blood vessels, leading to vasodilation and thus reducing peripheral vascular resistance. See also: Alfuzosin hydrochloride (salt form).

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Drug Indications
Alfuzosin is used to treat the signs and symptoms of benign prostatic hyperplasia (BPH).

FDA Label

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Mechanism of Action
α1-Adrenergic receptors are present in the prostate, bladder base, bladder neck, prostate capsule, and prostatic urethra; their activation can lead to smooth muscle contraction and cause urinary symptoms in patients with benign prostatic hyperplasia (BPH). Alfuzosin selectively binds to and inhibits α1-adrenergic receptors in the lower urinary tract. This leads to relaxation of the smooth muscle of the prostate and bladder neck, thereby improving urine flow and reducing urinary symptoms.
Alfuzosin hydrochloride is a quinazoline derivative α1-adrenergic blocker with a structure and pharmacological action related to prazosin. Alfuzosin is a non-subtype-specific α1-adrenergic blocker that selectively targets α1-adrenergic receptors in the lower urinary tract (e.g., bladder base, bladder neck, prostate, prostate capsule, prostatic urethra). Blocking these adrenergic receptors leads to relaxation of the smooth muscle of the bladder neck and prostate, thereby improving urine flow and reducing symptoms of benign prostatic hyperplasia (BPH).

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Therapeutic Use
Antihypertensive Drug
Alfuzosin hydrochloride is used to treat symptoms of benign prostatic hyperplasia (BPH). Alfuzosin can relieve moderate to severe irritative symptoms (such as urinary frequency, urgency, nocturia) and obstructive symptoms (such as urinary hesitation, interrupted or weak flow, incomplete emptying, or straining), and can significantly improve urinary flow rate in a significant proportion of patients.
Alfuzosin is not indicated for the treatment of hypertension. /Alfuzosin Hydrochloride/

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Drug Warnings
In a QT interval effect study of 45 healthy men, the QT interval prolongation caused by 10 mg alfuzosin appeared to be less than that caused by 40 mg, and the QT interval prolongation effect of 40 mg alfuzosin appeared to be less significant than that of the active control drug moxifloxacin at therapeutic doses. Although no evidence of torsades de pointes ventricular tachycardia has been found in extensive post-marketing experience outside the United States, this observation should be considered when prescribing Uroxatral in patients with a known history of QT prolongation or those taking medications known to prolong the QT interval. There are currently no pharmacokinetic/pharmacodynamic studies of the effects of other alpha-blockers on cardiac repolarization. Alfuzosin Hydrochloride: Orthostatic hypotension, with or without symptoms (e.g., dizziness), may occur within hours after administration of Uroxatral (alfuzosin hydrochloride extended-release tablets). As with other alpha-blockers, this product carries a risk of syncope. Patients should be informed of the possibility of such events and to avoid injury due to syncope. Uroxatral should be used with caution in patients with symptomatic hypotension or a history of hypotension with other medications. Prostate cancer and benign prostatic hyperplasia can cause many of the same symptoms. These two conditions often coexist. Therefore, patients suspected of having benign prostatic hyperplasia (BPH) should undergo examination to rule out prostate cancer before starting treatment with Eulotar (alfuzosin hydrochloride extended-release tablets). Eulotar should be discontinued if new angina symptoms develop or symptoms worsen. /Alfuzosin Hydrochloride Extended-Release Tablets/ For more complete data on drug warnings for alfuzosin (16 in total), please visit the HSDB record page.

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Pharmacodynamics
Alfuzosin alleviates BPH symptoms by selectively inhibiting α-adrenergic receptors in the lower urinary tract, relaxing the smooth muscle of the bladder neck and prostate, and improving urine flow. In addition, alfuzosin reduces the vasoconstrictive effects of catecholamines (adrenaline and noradrenaline), leading to peripheral vasodilation. This can result in a risk of orthostatic hypotension/syncope, and the prescribing information warns that caution should be exercised in patients taking nitrates, antihypertensive medications, or those who experience a drop in blood pressure after taking other medications.
Alfuzosin is an FDA-approved medication for the treatment of benign prostatic hyperplasia (BPH). It is marketed under various brand names. Its mechanism of action involves the selective and competitive antagonism of α1-adrenergic receptors in the prostate and bladder neck, leading to smooth muscle relaxation and improved urinary flow. It was first launched in France in 1988. Alfuzosin is not indicated for the treatment of hypertension. It is available in immediate-release and extended-release formulations. Its moderate protein binding and favorable side-effect profile compared to other α1-blockers make it a widely used treatment option for BPH.

C19H27N5O4

389.44878

389.206

81403-80-7

Alfuzosin hydrochloride;81403-68-1;Alfuzosin-d7;1133386-93-2;Alfuzosin-13C,d3;Alfuzosin-d3;1006724-55-5

2092

White to off-white solid powder

1.3±0.1 g/cm3

1.621

-1

2

8

8

28

511

0

WNMJYKCGWZFFKR-UHFFFAOYSA-N

InChI=1S/C19H27N5O4/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)

N-[3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]propyl]oxolane-2-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~128.39 mM)

Solubility in Formulation 1: ≥ 3 mg/mL (7.70 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 30.0 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.

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Solubility in Formulation 2: ≥ 3 mg/mL (7.70 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 30.0 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.

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Solubility in Formulation 3: ≥ 3 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)