The Alpha Adrenergic Binding Properties of Terazosin in the Human Prostate Adenoma and Canine Brain

Abstract

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 alpha1 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>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>0.05). The density of alpha1 (0.37 ± 0.15 fmol/mg. wet wt.) and alpha2 (0.29 ± 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p>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 μm., 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 μM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha1 adrenergic binding sites in the human prostate and canine brain. (J. Urol., 140: 664–667, 1988)