Pharmacological Options in the Treatment of Benign Prostatic Hyperplasia

Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead

“…When the benzoic acid substituent from the original hit was replaced with phenylacetic acid (8) or dihydrocinnamic acid (9), the potency remained the same. In contrast, the introduction of an ether linker to give a biphenyl group (10) led to an increase in the antagonist activity (IC 50 = 0.089 μM). Furthermore, the ortho-and meta-substituted carboxylic acid analogues 10 and 13 were more potent than the corresponding para-substituted derivatives (IC 50 = 0.14 μM for 13, 44% inhibition at 1 μM for 14).…”

“…One option for the treatment of BPH is to reduce the prostatic smooth muscle tone using α 1 adrenoceptor antagonists such as tamsulosin or doxazosin, which are currently used in clinical practice to contract the urethra. 10,11 We previously reported that LPAs can induce the contraction of the urethra via LPA 1 . Notably, LPAs have been reported to exhibit similar levels of contractile potency to the α 1 adrenoceptor agonist phenylephrine.…”

Safety and efficacy of tamsulosin in the treatment of painful ejaculation: a randomized, double-blind, placebo-controlled study

“…20 Electrophysiological study of prostate and smooth muscles have shown that the a 1A and a1L-adrenoceptor subtype predominates in the prostate capsule and it is responsible for mediating smooth muscle tone. [21][22][23][24][25] Another study demonstrates that a 1 -adrenoceptors in the human detrusor are of the a 1D and, to a lesser extent, the a 1A subtypes. 26 Tamsulosin is an a 1 -adrenoceptor antagonist that exhibits selectivity for a 1A -and, somewhat lesser extent, a 1D -over a 1B -adrenoceptors.…”

Relationship between lower urinary tract symptoms and urinary ATP in patients with benign prostatic hyperplasia or overactive bladder

“…Alpha-1 adrenergic receptor antagonists are the firstline medications for the treatment of benign prostatic hyperplasia (BPH), because these drugs relax the smooth muscle in the prostate and decrease resistance to urine flow in the prostatic urethra (6,10). These antagonists improve both urinary voiding disorders and urinary collecting disorders, while coadministration of the alpha-1 adrenergic receptor antagonist and the anti-muscarinic agent is more effective for controlling overactive bladder (OAB) in BPH patients (3).…”