1 One of the most common, but by no means the only, cause of male LUTS is benign prostatic hyperplasia (BPH), the stromoglandular hyperplasia of the prostate gland that develops after age 40 in the majority of men, and is present on tissue samples in about 50% of all men over the age of 50 years.2 At least as frequently is the bladder the source of male LUTS; symptoms of overactive bladder (urgency, frequency, Inhibitors,research,lifescience,medical nocturia, and urge urinary incontinence) are

as common in men as they are in women, although they are less often labeled as such and more often treated as BPH-related symptoms in men.3 Due to the increase in life expectancy worldwide, and the aging of the Baby Boom Generation in the United States, a considerable increase in the population of men seeking care for male LUTS is forecast that will require adjustments on the part of the health care provider and cost-effective management Inhibitors,research,lifescience,medical algorithms.4 Whereas in decades past the only available treatment option was a transurethral resection of the prostate, in the past 20 years medical therapy has established itself firmly as a viable and cost-effective alternative

for the majority of men.5,6 In addition to the 2 major classes of drugs, the α-adrenergic receptor blockers (or Inhibitors,research,lifescience,medical α-blockers) and the 5α-reductase inhibitors, antimuscarinics, phytotherapeutic agents, and combinations thereof are in widespread use. None, however, are more often used than α-blockers, which were introduced Inhibitors,research,lifescience,medical for the treatment of male LUTS in the early 1990s.7 α1-Adrenergic Receptors Adrenergic receptors (ARs) were originally divided into α-AR and β-AR categories,8

but application of molecular biologic methods has confirmed 9 total AR subtypes: α1A (formerly named α1C), α1B, α1D, α2A, α2B, α2C, β1, β2, and β3.9 α1 ARs generally mediate their actions through members of the Gq/11 family of G proteins that stimulate inositol phosphate Inhibitors,research,lifescience,medical (membrane phospholipid) hydrolysis, with each subtype demonstrating different Adenosine efficacy of coupling to phosphoinositide hydrolysis: α1A > α1B > α1D.10 In addition, α1-AR CI-1033 price subtypes can be pharmacologically distinguished on the basis of differential binding to α1-antagonists (blockers),11 as well as differential inactivation by the alkylating agent chloroethylclonidine.10,12 Tissue Distribution of α1-Adrenoceptor Subtypes All 3 α1-AR subtypes exist in a wide range of human tissues.13 The α1A-AR subtype shows highest levels of expression in human liver, followed by slightly lower levels in heart, cerebellum, and cerebral cortex; the α1B-AR subtype has highest expression in human spleen, kidney, and fetal brain; α1D-AR has highest levels in the cerebral cortex and human aorta.