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Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models.
Eur J Pharmacol. 2011 Nov 01; 669(1-3):84-93.EJ

Abstract

The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥ 10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent.

Authors+Show Affiliations

Metabolic Disease Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Osaka, Japan. kusumoto_keiji@takeda.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

21816148

Citation

Kusumoto, Keiji, et al. "Antihypertensive, Insulin-sensitising and Renoprotective Effects of a Novel, Potent and Long-acting Angiotensin II Type 1 Receptor Blocker, Azilsartan Medoxomil, in Rat and Dog Models." European Journal of Pharmacology, vol. 669, no. 1-3, 2011, pp. 84-93.
Kusumoto K, Igata H, Ojima M, et al. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. Eur J Pharmacol. 2011;669(1-3):84-93.
Kusumoto, K., Igata, H., Ojima, M., Tsuboi, A., Imanishi, M., Yamaguchi, F., Sakamoto, H., Kuroita, T., Kawaguchi, N., Nishigaki, N., & Nagaya, H. (2011). Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. European Journal of Pharmacology, 669(1-3), 84-93. https://doi.org/10.1016/j.ejphar.2011.07.014
Kusumoto K, et al. Antihypertensive, Insulin-sensitising and Renoprotective Effects of a Novel, Potent and Long-acting Angiotensin II Type 1 Receptor Blocker, Azilsartan Medoxomil, in Rat and Dog Models. Eur J Pharmacol. 2011 Nov 1;669(1-3):84-93. PubMed PMID: 21816148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. AU - Kusumoto,Keiji, AU - Igata,Hideki, AU - Ojima,Mami, AU - Tsuboi,Ayako, AU - Imanishi,Mitsuaki, AU - Yamaguchi,Fuminari, AU - Sakamoto,Hiroki, AU - Kuroita,Takanobu, AU - Kawaguchi,Naohiro, AU - Nishigaki,Nobuhiro, AU - Nagaya,Hideaki, Y1 - 2011/07/28/ PY - 2010/12/21/received PY - 2011/06/27/revised PY - 2011/07/07/accepted PY - 2011/8/6/entrez PY - 2011/8/6/pubmed PY - 2012/2/9/medline SP - 84 EP - 93 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 669 IS - 1-3 N2 - The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥ 10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/21816148/Antihypertensive_insulin_sensitising_and_renoprotective_effects_of_a_novel_potent_and_long_acting_angiotensin_II_type_1_receptor_blocker_azilsartan_medoxomil_in_rat_and_dog_models_ DB - PRIME DP - Unbound Medicine ER -