Silodosin
[CAS# 160970-54-7]

Identification

• Classification: Biochemical >> Inhibitor >> Neuronal signaling >> Adrenergic receptor antagonist
• Name: Silodosin
• Synonyms: 1-(3-Hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2,3-dihydro-1H-indole-7-carboxamide; KAD 3213; KMD 3213; Urief
• Molecular Formula: C₂₅H₃₂F₃N₃O₄
• Molecular Weight: 495.53
• CAS Registry Number: 160970-54-7
• EC Number: 814-909-2
• SMILES: C[C@H](CC1=CC2=C(C(=C1)C(=O)N)N(CC2)CCCO)NCCOC3=CC=CC=C3OCC(F)(F)F

Properties

• Solubility: 10 mM (DMSO), <1 mg/mL (water) (Expl.)
• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.552, Calc.^*
• Boiling Point: 601.4±55.0 °C (760 mmHg), Calc.^*
• Flash Point: 317.5±31.5 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07;GHS08 Danger
• Risk Statements: H300-H302-H315-H318-H335-H361-H373-H412-H413
• Safety Statements: P203-P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P354+P338-P317-P318-P319-P321-P330-P332+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Acute toxicity	Acute Tox.	1	H300
Skin irritation	Skin Irrit.	2	H315
Serious eye damage	Eye Dam.	1	H318
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Silodosin is a selective alpha-1 adrenergic antagonist primarily used in the treatment of benign prostatic hyperplasia (BPH). BPH is a condition characterized by an enlarged prostate, which can lead to urinary difficulties such as increased frequency, urgency, and incomplete bladder emptying. Silodosin works by relaxing the muscles in the prostate and bladder neck, which helps to improve urinary flow and reduce symptoms associated with BPH.

Silodosin was first developed in Japan and introduced to the market in the mid-2000s. It is marketed under the trade name Rapaflo in the United States and other regions, primarily for the treatment of lower urinary tract symptoms related to BPH. The drug belongs to a class of medications known as selective alpha-1a blockers, which specifically target the alpha-1a receptors found in the smooth muscle of the prostate and bladder neck. This selectivity provides a more targeted approach to alleviating urinary symptoms with fewer side effects than non-selective alpha-1 blockers.

The discovery of silodosin stemmed from the need for more specific treatments for BPH that would minimize side effects, particularly those related to cardiovascular complications, such as orthostatic hypotension. Traditional non-selective alpha-1 blockers, such as prazosin, work by blocking alpha-1 receptors throughout the body, including in blood vessels, which can lead to lower blood pressure and other cardiovascular effects. Silodosin, by targeting only the alpha-1a receptors, reduces the risk of these systemic side effects, making it a preferred treatment option for many patients with BPH.

The pharmacological action of silodosin is based on its ability to bind selectively to the alpha-1a adrenergic receptors in the prostate and bladder, causing smooth muscle relaxation in these areas. This helps to relieve the pressure on the urethra and improve the flow of urine, which leads to a reduction in urinary frequency, urgency, and nocturia (frequent urination at night). Silodosin’s high specificity for alpha-1a receptors also means it has a relatively low risk of causing hypotension, a common side effect of other alpha-1 blockers.

Silodosin is usually administered in the form of a capsule, taken once daily, and is typically well tolerated. Common side effects include dizziness, headache, and retrograde ejaculation, which is a condition where semen flows backward into the bladder rather than being expelled through the urethra during ejaculation. Despite this, silodosin remains a widely prescribed drug due to its effectiveness and favorable safety profile compared to other treatments for BPH.

Beyond BPH, research into the potential uses of silodosin continues. There is ongoing investigation into its application in other disorders involving smooth muscle relaxation, such as bladder outlet obstruction and certain forms of urinary incontinence. Furthermore, studies are being conducted to explore its potential benefits in treating conditions such as chronic pelvic pain syndrome and overactive bladder.

In addition to its use in treating BPH, silodosin has been studied for its possible role in improving symptoms in patients with prostatitis, a condition involving inflammation of the prostate. Although silodosin is not specifically approved for prostatitis, its ability to relax prostate smooth muscle has made it a candidate for off-label use in this area.

In conclusion, silodosin represents an important advancement in the management of benign prostatic hyperplasia. By selectively targeting the alpha-1a adrenergic receptors, it provides significant therapeutic benefits with a reduced risk of side effects compared to non-selective alpha-1 blockers. Its continued research may lead to additional applications in other urological and pelvic conditions, solidifying its role as a valuable medication in the field of urology.

References

1995. KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. Molecular Pharmacology, 48(2), 250-258.
DOI: 10.1016/s0026-895x(25)10243-5

2024. Drugs to affect the smooth musculature of the human ureter - an update with integrated information from basic science to the use in medical expulsion therapy (MET). World Journal of Urology, 42, 5368-5375.
DOI: 10.1007/s00345-024-05368-5

1997. KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the functional alpha1-adrenoceptor in human prostate. European Journal of Pharmacology, 331(1), 39-47.
DOI: 10.1016/s0014-2999(97)01009-1