Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned α₁‐adrenoceptor subtypes and in human prostate

Abstract

1. We have previously shown that among alpha 1-adrenoceptor antagonists used or investigated for the treatment of benign prostatic hyperplasia, tamsulosin discriminates alpha 1-adrenoceptor subtypes in rat tissues whereas alfuzosin and naftopidil do not. We now expand these studies to additional drugs (doxazosin, terazosin) being used and/or investigated for this purpose, and have evaluated all of these drugs at cloned subtypes and in human prostate. 2. Competition binding studies were performed with [3H]-prazosin in membrane samples from rat spleen, kidney and cerebral cortex and human prostate and with cloned alpha 1-adrenoceptors expressed in COS cells. Doxazosin and terazosin did not discriminate alpha 1-adrenoceptor subtypes in rat kidney and cerebral cortex. In contrast, the subtypes present in the tissues were well discriminated by the alpha 1A-adrenoceptor-selective reference drug WB 4101. 3. Alfuzosin, doxazosin, naftopidil and terazosin did not discriminate cloned alpha 1-adrenoceptor subtypes transiently expressed in COS cells whereas tamsulosin and WB 4101 did. 4. In human prostate, alfuzosin, doxazosin, naftopidil and terazosin did not discriminate the alpha 1-adrenoceptor subtypes present in this tissue whereas tamsulosin and the alpha 1A-adrenoceptor-selective reference drugs WB 4101, phentolamine and 5-methylurapidil did. Based on data with the alpha 1A-adrenoceptor-selective drugs, human prostate contains alpha 1A- and alpha 1B-adrenoceptors in an approximate 70:30% ratio. 5. We conclude that tamsulosin, in common with WB 4101, but in contrast to alfuzosin, doxazosin, naftopidil, and terazosin is selective for alpha 1A-adrenoceptors which appear to dominate in the human prostate; the therapeutic relevance of this selectivity remains to be assessed in clinical studies.

Ocular trauma caused by a loose slip-lock cannula during corneal hydration

“…1 Controversy exists over the receptor subtypes present in the prostate and the precise mechanism of action of this type of agents. [2][3][4] Recent experience in our unit is in accord with Chang's report; 1 the majority of patients treated with tamsulosin undergoing cataract surgery seem to display the features of IFIS. We have noted no benefit from the temporary cessation of treatment preoperatively.…”

“…2 Anti-IgG activity has also been identified in artery biopsy specimens. 3 Recently, a model for the pathogenesis of GCA proposed by Weymann and Goronzy 4 suggests a cell-mediated aetiology. Approximately 30% of patients with GCA have neurologic manifestations.…”

“…Iatrogenic orbital needle stick injuries have been reported, especially with sliplock systems where needles have become accidentally dislodged during procedures, some with sight threatening consequences. [1][2][3] This case report describes a situation where a slip-lock cannula dislodged under high pressure during the stromal hydration step of what was otherwise a routine cataract procedure. It entered the eye at high velocity and resulted in iris perforation, zonule rupture, hyphaema, and vitreous haemorrhage.…”

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

“…26 Tamsulosin is an a 1 -adrenoceptor antagonist that exhibits selectivity for a 1A -and, somewhat lesser extent, a 1D -over a 1B -adrenoceptors. [26][27][28][29] In addition, tamsulosin has 12 times greater affinity for a 1 -adrenoceptors in the human prostate than in the aorta in contrast to prazosin, which has comparable affinity for those in the prostate and aorta. 30 This can be referred to as receptor pharmacological uroselectivity.…”

Alpha–1–adrenoceptor blockade in the treatment of benign prostatic hyperplasia

“…27 ± 34 While some analyses indicate that tamsulosin is weakly selective for the alpha-1A subtype vs alpha-1B, 29,33 others report that none of the four agents has subtype selectivity. 27,28,31 The consensus opinion of the Alpha-Blocker Committee at the 4th International Consultation on BPH was that none of these agents has any distinct selectivity for alpha-1-adrenoceptor subtypes nor for the prostate that could be indicative of clinical selectivity.…”