α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms

Background: Although α1 adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by cardiovascular-related side effects that are caused by the subtype nonselective nature of many current drugs. To overcome this problem, it was hypothesized that an α1a/1d subtype selective antagonist would be efficacious yet produce less side effects, and hence would bring greater benefit for the therapy of BPH/LUTS. Unfortunately, such highly selective α1a/1d antagonists were not available, making the validation of the new hypothesis impossible. Objective/method: This review disclosed several series of α1a/1d subtype selective antagonists that have been discovered and developed by Johnson & Johnson recently. These compounds show equal and potent affinity for both α1a and α1d subtypes with good selectivity versus the α1b subtype. Some analogues also possess favorable pharmacokinetic properties. Conclusion: Although discovery of α1a/1d subtype selective antagonists paves the way for future research, the effectiveness of α1a/1d subtype selective antagonist in BPH/LUTS patients still needs to be proven in clinical trials. This patent review will focus on the latest progress in this field from 2006 to present.

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