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α1-adrenergic receptor signaling has been implicated in cancer progression through the stimulation of cell proliferation, cell migration and cell invasion. Conversely, blocking α1-adrenergic recept...

This paper was published as BJU International, 2006, 97 (2), pp. 329-332. It is available from http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-410X. Doi: 10.1111/j.1464-410X.2006.05956.x

The synthesis and preliminary characterization of three radioiodinated α1-adrenergic receptor ligands [125I]5a–c are described. These tracers are analogs of L-760,478, 1b, itself an analog of prazosin, 1a. The highest affinity tracer, [125I]5a, has six fold higher affinity for the α1 receptor subtypes than prazosin. These ligands could be useful for autoradiographic studies of the α1 receptor subtypes. Copyright © 2001 John Wiley & Sons, Ltd.

Pharmacological and molecular biological studies have revealed heterogeneity among α1 adrenoceptor subtypes. Pharmacological agents used to characterize these sites often possess only moderate selectivity for a particular α1 adrenoceptor or have effects on other adrenergic or nonadrenergic receptors. Cloning studies have identified distinct amino acid sequences for three subtypes of α1 adrenoceptor, although the pharmacological characteristics of expressed receptors did not always coincide with expectations. As a result, controversial and alternate classification concepts have emerged that propose different numbers of α1 adrenoceptors or different naming conventions. Recent advances with an increasing variety of more selective compounds have resulted in an emerging consensus that identifies three subtypes of α1 adrenoceptor. The pharmacological and molecular biological studies that have contributed to or promoted resolution of these controversies are discussed in this review. Drug Dev. Res. 39:54–107. © 1997 Wiley-Liss, Inc.

The quantitative structure-activity relationship (QSAR) has been studied for the derivatives of 3-aryl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridine for their in vitro ability to displace [ 3 H]prazosin. The physicochemical parameters, hydrophobic (π), and electronic (σ), and the structural parameter, van der Waals volume (V W ) are found to be significantly correlated with the displacement activity of these compounds

A novel series of aryl piperazine substituted heterocycles has been synthesized and identified as antagonists of the α 1a -adrenergic receptor (α 1a -AR), which has been implicated in benign prostatic hyperplasia (BPH). These compounds selectively inhibit binding to the α 1a -AR with K i s as low as 2.1 nM.

Short-term receptor regulation by agonists is a well-known phenomenon for a number of receptors but little is known about the regulation of alpha 1-adrenergic receptors. In the present study we provide evidence of alpha 1-adrenergic receptor changes induced by agonists on DDT1 MF-2 smooth muscle cells. The cells were preincubated with the agonist and receptor changes were investigated in the cells washed free of the agonist. On cells pretreated with norepinephrine the number of receptors recognized by [3H]prazosin at 4 degrees C was reduced by 38%. The receptors were not degraded as the number of sites was the same in control and norepinephrine-treated cells when binding was measured at 37 degrees C. When binding was measured on fragmented membranes (at 4 degrees C), the number of receptors was the same in control and norepinephrine-treated cells, suggesting that the disruption of cellular integrity might expose receptors which are probably sequestered after agonist treatment. We conclude that agonists induced rapid sequestration of receptors on intact DDT cells.

In a preliminary experiment in 12 healthy volunteers, one drop of thymoxamine 0.5% instilled into the conjunctival sac completely reversed the mydriasis produced by phenylephrine 2.5%, 5% and 10% after 20 minutes. In a second study in eight volunteers, thymoxamine 0.5% completely prevented the mydriasis produced by phenylephrine 2.5% and produced a miosis. It also completely reversed the mydriasis produced by tropicamide 0.5%. The mydriatic effect of tropicamide 0.5% plus phenylephrine 2.5%, however, was not completely reversed by thymoxamine 0.5% over a period of 180 minutes. Phenylephrine, tropicamide and thymoxamine are freely available for use by registered optometrists.

Gastric emptying, small intestinal transit, and colonic transit were measured in fasted rats preimplanted with either duodenal or colonic cannulae. At the doses stated, prazosin (given subcutaneously) had no effect on gastric emptying or colonic transit, whereas small intestinal transit was significantly delayed.