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

Muscarinic Receptor Binding Characteristics in Rat Tissues after Oral Administration of Oxybutynin and Propiverine.

“…The technique of ex vivo and in vivo receptor binding is useful for predicting the in vivo potency, organ selectivity, and duration of action of drugs in relation to their pharmacokinetics and pharmacodynamics. [10][11][12][13][14][15] In the present study, the ex vivo receptor binding technique was used to simultaneously examine mucarinic receptor binding characteristics in the bladder and other tissues of rats after systemic administration of oxybutynin and propiverine. The oral doses of oxybutynin and propiverine chosen were 50.8 or 127 mmol/kg and 24.8- Values are meanϮS.E.…”

“…10) This was the case for the receptor binding properties of the 1,4-dihydropyridine calcium channel antagonists 11,12) and a 1 -adrenoceptor antagonists. [13][14][15] Thus, the aim of the present study was to characterize the muscarinic receptor binding in rat tissues, such as the bladder, after oral administration of oxybutynin and propiverine, the most commonly used anticholinergic agents for the treatment of patients with detrusor instability and detrusor hyperreflexia. 3.09 TBq/mmol) was purchased from Dupont-NEN Co., Ltd. (Boston, MA, U.S.A.).…”

Relationship between the Functional Effect of Tamsulosin and Its Concentration in Lower Urinary Tract Tissues in Dogs

“…In rats, tamsulosin showed sustained occupancy of a 1 -adrenoceptors in the prostate after a marked reduction in plasma concentration. 22) One explanation for this retention of tamsulosin may be its characteristic binding kinetics action on the a 1 adrenoceptor subtype of prostate and urethra, namely a 1A adrenoceptors. In fact, an in vitro functional study suggested that equilibration of the effect of tamsulosin requires time in the human prostate (a 1A receptors) but not in the rat spleen (a 1B receptors) or rat aorta (a 1D receptors).…”

Prediction of .ALPHA.1-Adrenoceptor Occupancy in the Human Prostate from Plasma Concentrations of Silodosin, Tamsulosin and Terazosin to Treat Urinary Obstruction in Benign Prostatic Hyperplasia

“…DISCUSSION a 1 -Adrenoceptor occupancy in the human prostate was predicted from plasma unbound concentrations after a single oral administration of clinically effective dosages of silodosin, tamsulosin, and terazosin in healthy volunteers. a 1 -Adrenoceptor binding affinities (pK i ) of a 1 -adrenoceptor antagonists in the rat prostate 20) correlated significantly with those in the human prostate (Fig. 6).…”

“…Considering the prediction that prostatic a 1 -adrenoceptor occupancy would be more than 40% 12 and/or 24 h after oral administration of silodosin (8.1 mmolϫ2/d), tamsulosin (0.45 mmol/d), and terazosin (1.1 mmolϫ2/d) at 20) and pK i values in the human prostate were cited from Yamada et al 5,18,19) and Shibata et al 8) The pK i values for the inhibition by prazosin and tamsulosin of specific [ 3 H]tamsulosin in rat prostate were 9.89 and 10.4, respectively, and the pK i value for the inhibition by silodosin of specific [ 3 H]prazosin binding in rat prostate was 9.46 (our unpublished data). The points fit the equation yϭ0.85xϩ1.28, rϭ0.89 (pϽ0.05), where y, x, and r are pK i values in the human prostate, pK i values in rat prostate, and correlation coefficient, respectively.…”