Ex vivo occupancy by tamsulosin of α1-adrenoceptors in rat tissues in relation to the plasma concentration

Abstract At 0.5–12 h after oral administration of tamsulosin (2.3 μmol/kg) in rats, there was a significant decrease in specific [ 3 H]prazosin binding in the prostate as compared to the control value. The greater decrease occurred in the submaxillary gland. The effect of tamsulosin was mainly due to a marked reduction of [ 3 H]prazosin binding sites (Bmax) rather than to an increase in the dissociation constant (Kd). In contrast, there was only a slight decrease or no change in the [ 3 H]prazosin binding in the spleen, heart, and cerebral cortex of tamsulosin-administered rats at 0.5–12 h. Oral administration of terazosin (21.7 μmol/kg) significantly increased Kd values for [ 3 H]prazosin binding with little effect on Bmax values in the rat prostate at 3 and 6 h. The greater increases in Kd values were observed in the submaxillary gland, spleen and heart at 0.5–12 h. Terazosin had a slight effect on Kd values for the cerebral cortical [ 3 H]prazosin binding. Tamsulosin was absorbed rapidly after oral administration at a dose of 2.3 μmol/kg in rats, and at 6 h, plasma concentration decreased markedly to approximately one-twentieth of the 0.5 h peak level. α 1 -Adrenoceptor occupancy was estimated as a percentage of decrease in Bmax values for [ 3 H]prazosin binding in tissues of tamsulosin-treated rats compared with control rats. The α 1 -adrenpceptor occupancy by tamsulosin in the prostate and submaxillary gland occurred rapidly in parallel with the rise in plasma concentration of tamsulosin, and lasted for over 12 h despite the marked decrease in plasma concentration. Consequently, it is suggested that tamsulosin produces more selective and sustained occupancy in vivo of α 1 -adrenoceptors in the submaxillary gland and prostate of rats than in other tissues.