Drugs online research references
Life Sci. 1998;63(24):2147-55.
Ex vivo occupancy by tamsulosin of alpha1-adrenoceptors in rat tissues in relation to the plasma concentration.
Ohkura T, Yamada S, Deguchi Y, Kimura R, Matsushima H, Higuchi S, Inagaki O, Honda K, Takenaka T.
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9851306&dopt=Abstract
J Med Chem. 1998 Dec 17;41(26):5320-33.
Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia.
Nagarathnam D, Wetzel JM, Miao SW, Marzabadi MR, Chiu G, Wong WC, Hong X, Fang J, Forray C, Branchek TA, Heydorn WE, Chang RS, Broten T, Schorn TW, Gluchowski C.
Departments of Chemistry, Pharmacology, and Pharmaceutical Operations, Synaptic Pharmaceutical Corporation, Paramus, New Jersey 07652, USA.
We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9857099&dopt=Abstract
Jpn J Pharmacol. 1998 Nov;78(3):331-5.
Tamsulosin: alpha1-adrenoceptor subtype-selectivity and comparison with terazosin.
Muramatsu I, Taniguchi T, Okada K.
Department of Pharmacology, School of Medicine, Fukui Medical University, Matsuoka, Japan.
Selectivity of tamsulosin and terazosin to functional alpha1-adrenoceptors was examined. Both drugs competitively inhibited the contractile responses to noradrenaline in different tissues where the responses were mediated through the alpha1D-, alpha1B- or alpha1L-subtype. Together with the affinities obtained in the binding study with cloned (alpha1a, alpha1b, alpha1d) and native (alpha1A and alpha1B) subtypes, the selectivity of tamsulosin was alpha1A>alpha1L, alpha1D>alpha1B. Terazosin had lower affinity at various subtypes than tamsulosin, but showed relatively high selectivity to the alpha1D-subtype. In the human prostate, tamsulosin was more than 30-fold higher in affinity than terazosin in functional and binding studies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9869267&dopt=Abstract
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Wellstreet online pharmacy for click-order prescription medications ||
Altace Online Pharmacy ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Insurance plans and information ||
Insurance policies for all purposes ||
Antibiotics and prescription medications online literature ||