α1-adrenergic receptor
α1-adrenergic receptor (α1-AR) subtypes, with highest affinity for α1A-AR (Ki = 0.034 nM) and α1D-AR (Ki = 0.23 nM), lower affinity for α1B-AR (Ki = 4.5 nM) [1]
- α1A- and α1D-adrenergic receptors, which mediate smooth muscle contraction in the prostate and vasculature [2]

In vitro activity: Tamsulosin is a α1 receptor antagonist that exhibits selectivity towards the α1A receptor in the prostate as opposed to the α1B receptor in blood vessels. Compared to control patients, patients on tamsulosin had a 0.30-fold decreased risk of experiencing acute urinary retention. There were no appreciable differences in any of the male questionnaire domain scores from the International Continence Society between the groups. When treating men for AUR following catheterization, tamsulosin may be suggested as it can lower the chance of re-catheterization.

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Tamsulosin HCl competitively inhibited [3H]-prazosin binding to α1-AR subtypes in human prostate membrane preparations, with selective antagonism of α1A- and α1D-AR over α1B-AR [1]
- Tamsulosin HCl suppressed angiotensin II-induced proliferation and migration of mouse aortic smooth muscle cells (ASMCs) by inhibiting the PI3K/Akt/mTOR signaling pathway; it also reduced collagen type I and matrix metalloproteinase-9 (MMP-9) expression in ASMCs [2]

Tamsulosin exhibits high plasma-protein binding, largely to α1-acid glycoprotein. Eighteen to fifteen percent of an oral dose is eliminated by the kidneys as the parent compound after it is metabolized, mostly by cytochrome P450 (CYP) 3A4 and CYP2D6 to low abundance compounds. The pharmacokinetics of tamsulosin are not affected to a major extent by age, and pharmacokinetic alterations in renally impaired patients relate largely to an increased concentration of α1-acid glycoprotein. Medication adjustment is not necessary for either mild to moderate hepatic impairment or renal impairment because pharmacokinetic changes associated with hepatic impairment are only moderate. Tamsulosin was quickly absorbed after oral administration (within 30 to 90 minutes) in early studies involving rats and dogs, but its absolute bioavailability was only 7–23% in rats and 30–42% in dogs. Tamsulosin MR has a near-100 percent absolute bioavailability in humans who are fasting. In the fed state, the tmax is approximately 6 hours (range 5.2-7.0 hours), and in the fasted state, it is usually about 5 hours (reported range of mean values 2.9-5.6 hours). Animal studies involving intravenous injection of radiolabelled tamsulosin and measurement of radiolabel in various tissues after 10 minutes have shown the presence of the drug in various tissues, ranked in the following order: kidney>lung≈heart>submaxillary gland>liver ≈spleen≈aorta≈vas deferens> prostate>>cerebral cortex, the latter being close to detection limits. The blood-brain barrier might not be crossed by tamsulosin. In rats and dogs, tamsulosin is extensively metabolized in the liver, and the parent compound is excreted in the urine at rates of 1.2% and 2.8%, respectively. While rats and dogs also experience extensive hepatic metabolism, it appears that humans experience this process to a lesser extent, as 8.7–15% of an oral dose is eliminated in the urine in an unmetabolized form. Tamsulosin is eliminated from the body at varying rates depending on the species. For example, rats and dogs eliminate tamsulosin from their bodies more quickly than humans do.

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In rats with benign prostatic hyperplasia (BPH), Tamsulosin HCl (0.01-0.1 mg/kg, oral) reduced intraurethral pressure and improved urinary flow rate by relaxing prostatic and bladder neck smooth muscle [1]
- In ApoE-/- mice with angiotensin II-induced abdominal aortic aneurysm (AAA), Tamsulosin HCl (0.1 mg/kg/day, oral gavage for 28 days) attenuated AAA growth (reduced maximal aortic diameter by 31.2%) and decreased aortic wall inflammation, elastin degradation, and smooth muscle cell loss [2]

Membrane preparations from human prostate tissue were incubated with [3H]-prazosin (radioligand) and various concentrations of Tamsulosin HCl for 60 minutes at 25°C. Bound and free ligands were separated by filtration, and radioactivity was measured to determine binding affinity (Ki values) for α1-AR subtypes [1]
- α1-AR subtype-specific radioligand binding assays were performed using recombinant human α1A-, α1B-, and α1D-AR-expressing cell membranes; competition curves were generated to calculate IC50 values and subtype selectivity ratios [1]

Mouse ASMCs were isolated from aortic tissue and cultured in DMEM supplemented with fetal bovine serum. Cells were pretreated with Tamsulosin HCl (1-10 μM) for 1 hour, then stimulated with angiotensin II (100 nM) for 24-48 hours. Cell proliferation was assessed by CCK-8 assay, migration by Transwell assay, and protein expression (PI3K, Akt, mTOR, MMP-9) by Western blot [2]
- Collagen type I secretion by ASMCs was measured using enzyme-linked immunosorbent assay (ELISA) after 48 hours of treatment with Tamsulosin HCl and angiotensin II [2]

Dissolved in saline; 0.1 and 1 μg/kg; s.c. injection
Female Wistar rats

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BPH model rats (induced by testosterone propionate injection) were randomly divided into control and treatment groups. Tamsulosin HCl was administered orally at doses of 0.01, 0.03, and 0.1 mg/kg once daily for 2 weeks. Urinary flow parameters and intraurethral pressure were measured under anesthesia [1]
- ApoE-/- mice (8-10 weeks old) were implanted with osmotic minipumps delivering angiotensin II (1000 ng/kg/min) to induce AAA. Tamsulosin HCl was dissolved in normal saline and administered via oral gavage at 0.1 mg/kg/day for 28 days. Mice were euthanized, and aortic tissues were collected for histopathological and molecular analysis [2]

Tamsulosin hydrochloride has an oral bioavailability of approximately 90% in humans (food has no significant effect on absorption). Peak plasma concentration (Cmax) is reached 0.5–1 hour after oral administration [1]
- Plasma protein binding is 99%, mainly bound to albumin and α1-acid glycoprotein [1]
- Tamsulosin hydrochloride is metabolized in the liver by cytochrome P450 (CYP) enzymes, mainly by CYP3A4 and CYP2D6 to inactive metabolites [1]
- The elimination half-life (t1/2) in humans is 10–14 hours; approximately 70% of the dose is excreted in the urine (10% of which is the original drug), and 20% is excreted in the feces [1]

Common adverse reactions in humans include dizziness (6.3%), orthostatic hypotension (3.2%), rhinitis (2.8%), and ejaculatory abnormalities (2.1%); these adverse reactions are dose-related and are generally mild to moderate [1]
- No significant hepatotoxicity or nephrotoxicity was observed in clinical trials; repeated daily administration did not lead to plasma concentration accumulation [1]
- In animal toxicity studies, high doses (100 times the therapeutic dose) caused hypotension and bradycardia, but no fatal toxicity was reported [1]

[1]. Tamsulosin: an overview. World J Urol. 2002 Apr;19(6):397-404.

[2]. Tamsulosin Attenuates Abdominal Aortic Aneurysm Growth. Surgery. 2018 Nov; 164(5): 1087-1092.

Tamsulosin hydrochloride is the hydrochloride salt formed by the reaction of equimolar amounts of tamsulosin with hydrogen chloride. It is an alpha-adrenergic antagonist and antitumor drug. It contains the tamsulosin (1+) molecule. It is the enantiomer of ent-tamsulosin hydrochloride. Tamsulosin hydrochloride is the hydrochloride salt of tamsulosin, a sulfonamide derivative with adrenergic antagonistic activity. Tamsulosin selectively binds to and blocks the activity of alpha-1 adrenergic receptors in the human prostate and bladder neck; blocking these adrenergic receptors relaxes the smooth muscle of the prostate and bladder neck, thereby improving urinary flow rate. Tamsulosin hydrochloride is a sulfonamide derivative and alpha-1 adrenergic receptor antagonist used to relieve urinary tract obstruction symptoms caused by benign prostatic hyperplasia. See also: Tamsulosin (note moved to). Tamsulosin hydrochloride is a selective α1A/α1D adrenergic receptor antagonist approved for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)[1]. Its therapeutic effect is achieved by relaxing the smooth muscle of the prostatic interstitium and bladder neck, reducing urethral resistance and improving urinary flow rate[1]. Tamsulosin hydrochloride slows the growth of abdominal aortic aneurysms (AAA) by inhibiting smooth muscle cell proliferation/migration and reducing inflammation. It also protects the extracellular matrix of the aortic wall[2].

C20H28N2O5S.HCL

444.97

444.148

C, 55.00; H, 6.56; Cl, 8.54; N, 6.75; O, 15.42; S, 7.73

106463-17-6

Tamsulosin;106133-20-4; Tamsulosin-d5 hydrochloride; Tamsulosin-d4 hydrochloride; 2518100-55-3

5362376

White to off-white solid powder

595.5ºC at 760 mmHg

228-230ºC

313.9ºC

3.79E-14mmHg at 25°C

4.512

3

7

11

29

539

1

Cl[H].S(C1=C(C([H])=C([H])C(=C1[H])C([H])([H])[C@@]([H])(C([H])([H])[H])N([H])C([H])([H])C([H])([H])OC1=C([H])C([H])=C([H])C([H])=C1OC([H])([H])C([H])([H])[H])OC([H])([H])[H])(N([H])[H])(=O)=O

ZZIZZTHXZRDOFM-XFULWGLBSA-N

InChI=1S/C20H28N2O5S.ClH/c1-4-26-17-7-5-6-8-18(17)27-12-11-22-15(2)13-16-9-10-19(25-3)20(14-16)28(21,23)24;/h5-10,14-15,22H,4,11-13H2,1-3H3,(H2,21,23,24);1H/t15-;/m1./s1

5-[(2R)-2-[2-(2-ethoxyphenoxy)ethylamino]propyl]-2-methoxybenzenesulfonamide;hydrochloride

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)