Tasosartan blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the AT1 receptor that mediates most, if not all, of the important actions of Ang II. Tasosartan binds reversibly to the AT1 receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. AT1 receptor antagonists avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors. Antagonism of the AT1 receptor with tasosartan reduces blood pressure at rest and during submaximal exercise but not during maximal exercise. The reduced blood pressure was associated with a reduced total peripheral resistance during submaximal exercise but not at rest in the control condition while cardiac output was unaltered in either condition. Lastly, tasosartan did not impair working capacity as measured from peak workload and oxygen uptake.
|Source||J Pharmacol Exp Ther (2000). Figure 4. Tasosartan|
|Method||receptor binding assay|
|Cell Lines||vascular smooth muscle cell|
|Incubation Time||4 to 6 h|
|Results||In the receptor binding assay, the addition of 6.25% human plasma to the buffer (final concentration of plasma protein 0.4%) resulted in small but significant differences in the affinity of tasosartan for the AT1 receptor (IC50 shifted from 2.0 to 9.5 nM), whereas the same procedure shifted IC50 for enoltasosartan from 0.4 to 340 nM|
|Source||J Pharmacol Exp Ther (2000). Figure 2. Tasosartan|
|Incubation Time||8.0 h|
|Results||Tasosartan was rapidly absorbed after oral administration and Tmax 30 min (with Cmax of 1596 ± 250 ng/ml) was observed in all subjects (n=12).|
|Administration||p.o. or i.v.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects.
Elokdah HM, et al. Bioorg Med Chem Lett. 2002 Aug 5;12(15):1967-71. PMID: 12113820.
Tasosartan, enoltasosartan, and angiotensin II receptor blockade: the confounding role of protein binding.
Maillard MP, et al. J Pharmacol Exp Ther. 2000 Nov;295(2):649-54. PMID: 11046101.
Angiotensin II-receptor antagonists: an overview.
Dina R, et al. Am J Health Syst Pharm. 2000 Jul 1;57(13):1231-41. PMID: 10902066.
A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension.
Andrawis NS, et al. J Clin Pharmacol. 2000 Mar;40(3):231-41. PMID: 10709151.
Effects of angiotensin antagonism with tasosartan on regional and systemic haemodynamics in hypertensive patients.
Rhéaume C, et al. J Hypertens. 1998 Dec;16(12 Pt 2):2085-9. PMID: 9886901.
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