EX-VIVO OCCUPANCY BY TAMSULOSIN OF ALPHA(1)-ADRENOCEPTORS IN RAT-TISSUES IN RELATION TO THE PLASMA-CONCENTRATION

At 0.5-12 h after oral administration of tamsulosin (2.3 mu mol/kg) in rats, there was a significant decrease in specific [H-3]prazosin bind ing in the prostate as compared to the control value. The greater decr ease occurred in the submaxillary gland. The effect of tamsulosin was mainly due to a marked reduction of [H-3]prazosin binding sites (Bmax) rather than to an increase in the dissociation constant (Kd). In cont rast, there was only a slight decrease or no change in the [H-3]prazos in binding in the spleen, heart, and cerebral cortex of tamsulosin-adm inistered rats at 0.5-12 h. Oral administration of terazosin (21.7 mu mol/kg) significantly increased Kd values for [H-3]prazosin binding wi th 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 va lues for the cerebral cortical [H-3]prazosin binding. Tamsulosin was a bsorbed rapidly after oral administration at a dose of 2.3 mu mol/kg i n rats, and at 6 h, plasma concentration decreased markedly to approxi mately one-twentieth of the 0.5 h Peak level, alpha(1)-Adrenoceptor oc cupancy was estimated as a percentage of decrease in Bmax values for [ H-3]prazosin binding in tissues of tamsulosin-treated rats compared wi th control rats. The alpha(1)-adrenoceptor 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 alpha(1)-adrenoceptors in the submaxillary gland and prostate of rats than In other tissues.