ALPHA-1-ADRENOCEPTOR PROPERTIES OF TERAZOSIN HCI AND ITS ENANTIOMERS IN THE HUMAN PROSTATE AND CANINE BRAIN

The objective of the present study was to characterize the alpha-1-adrenoceptor binding properties of terazosin and its enantiomers in human prostate and canine brain. Human prostate adenomas were obtained from 7 males undergoing prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from 6 male beagles. Competitive displacement experiments were carried out on these tissue homogenates in the presence of a constant concentration ([80 pM]) of I-125-Heat and varying concentrations of unlabelled terazosin and its enantiomers. The K(i) of terazosin and its enantiomers were determined from these binding studies. The mean K(i) of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in human prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between these mean K(i) values were not statistically significant. The mean K(i) of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in canine brain were 6.7 nM, 8.4 nM, and 5.6 nM, respectively. The differences between these mean K(i) values were not significantly different. The mean K(i) of terazosin and its enantiomers were consistently lower in the human prostate compared to canine brain (P < 0.05). The present study does not provide any evidence suggesting differential effects of terazosin enantiomers on the human prostate. The twofold difference between the K(i) values in the prostate and brain suggests that different subtypes of the alpha-1-receptor might be present in these tissues.