title: Ex vivo occupancy by tamsulosin of alpha1-adrenoceptors in rat tissues in relation to the plasma concentration.
abstract: At 0.5-12 h after oral administration of tamsulosin (2.3 micromol/kg) in rats, there was a significant decrease in specific [3H]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 [3H]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 [3H]prazosin binding in the spleen, heart, and cerebral cortex of tamsulosin-administered rats at 0.5-12 h. Oral administration of terazosin (21.7 micromol/kg) significantly increased Kd values for [3H]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 [3H]prazosin binding. Tamsulosin was absorbed rapidly after oral administration at a dose of 2.3 micromol/kg in rats, and at 6 h, plasma concentration decreased markedly to approximately one-twentieth of the 0.5 h peak level. alpha1-Adrenoceptor occupancy was estimated as a percentage of decrease in Bmax values for [3H]prazosin binding in tissues of tamsulosin-treated rats compared with control rats. The alpha1-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 alpha1-adrenoceptors in the submaxillary gland and prostate of rats than in other tissues.
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohkura
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Deguchi
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Matsushima
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: O
authors.initials: O
authors.lastname: Inagaki
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
mesh_terms: D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000818:Animals; D008297:Male; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000077409:Tamsulosin; D014018:Tissue Distribution
chemical_list: D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; C041226:Terazosin; D000077409:Tamsulosin; D011224:Prazosin