2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone and Prostatic-Hyperplasia

In order to determine the localization of alpha 1-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [3H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [125I]-HEAT, but not so clear specific binding sites for [3H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitial beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of alpha 1-adrenoceptors.

Topics: Aged; Autoradiography; Humans; Iodine Radioisotopes; Male; Middle Aged; Phenethylamines; Prazosin; Prostate; Prostatic Hyperplasia; Receptors, Adrenergic, alpha; Tetralones; Tritium

Clinical trials are currently underway to evaluate the efficacy of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). Terazosin is a potent and selective alpha 1 adrenergic blocking agent structurally similar to prazosin. The alpha adrenergic binding properties of terazosin were studied in human prostate adenomas and canine brains using radioligand receptor binding methods. Saturation analyses were performed at varying concentrations of [125I]-Heat and [3H]rauwolscine [( 3H]Ra) in human prostate adenomas and canine brains. The binding of [125I]-Heat and [3H]Ra in the human prostates and canine brains was consistently saturable and of high affinity. The equilibrium dissociation constant (Kd) for [125I]-Heat binding in the canine brains and human prostate adenomas was 84.4 +/- 4.3 pM and 65.4 +/- 19.2 pM, respectively (p greater than 0.05). The (Kd) for [3H]Ra binding in the human prostate adenomas and canine brains was 1.21 +/- 0.23 nM and 1.52 +/- 0.28 nM, respectively (p greater than 0.05). The density of alpha 1 (0.37 +/- 0.15 fmol/mg. wet wt.) and alpha 2 (0.29 +/- 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p greater than 0.05). The IC50 corrected (IC50 corr) of terazosin for [125I]-Heat and [3H]Ra binding sites in the human prostate was 2.5 nM and 1.0 micron., respectively. The IC50 corr of terazosin for [125I]-Heat and [3H]Ra binding sites in the canine brain was 2.0 nM and 0.8 microM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha 1 adrenergic binding sites in the human prostate and canine brain.

Topics: Adrenergic alpha-Antagonists; Aged; Animals; Binding Sites; Binding, Competitive; Cerebral Cortex; Dogs; Humans; Male; Middle Aged; Phenethylamines; Prazosin; Prostatic Hyperplasia; Tetralones; Yohimbine