Silodosin Mechanism of Action
Silodosin works by selectively blocking alpha-1A adrenergic receptors in the prostate, bladder neck, and prostatic urethra, causing smooth muscle relaxation that improves urinary flow and reduces BPH symptoms. 1
Receptor Selectivity and Pharmacologic Action
Silodosin is a highly selective alpha-1A adrenergic receptor antagonist with substantially greater affinity for the alpha-1A subtype compared to the alpha-1B subtype (by a factor of 583-fold). 2, 3 This selectivity is clinically important because:
- Alpha-1A receptors are predominantly located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra 1
- Alpha-1B receptors mediate vascular smooth muscle tone and blood pressure regulation 2, 4
- By preferentially targeting alpha-1A receptors, silodosin minimizes cardiovascular side effects (particularly orthostatic hypotension) that result from alpha-1B blockade 2, 3, 5
Clinical Mechanism in BPH
The therapeutic effect occurs through the following pathway:
- Blockade of post-synaptic alpha-1A adrenergic receptors in prostatic and urethral smooth muscle 1
- Smooth muscle relaxation in the lower urinary tract 3, 4
- Reduction in bladder outlet obstruction 6
- Improvement in both voiding symptoms (weak stream, hesitancy) and storage symptoms (urgency, frequency) 3, 5
Important Clinical Distinctions
Unlike 5-alpha reductase inhibitors, silodosin does NOT reduce prostate volume—it purely addresses the dynamic component of obstruction through smooth muscle relaxation. 7 This means:
- Rapid onset of action (typically within 2-4 weeks) 7, 3
- Efficacy is independent of prostate size 7
- Does not prevent acute urinary retention or need for surgery long-term 7
Common Pitfall: Ejaculatory Dysfunction
The high alpha-1A selectivity that provides cardiovascular safety comes with a trade-off: retrograde or abnormal ejaculation occurs in >22% of patients 2, 8, which is higher than less selective alpha-blockers like terazosin. 6 This occurs because alpha-1A receptors also mediate seminal emission and bladder neck closure during ejaculation. 3, 5 However, few patients discontinue therapy for this reason. 8, 5