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Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, U-97018.
J Pharmacol Exp Ther. 1995 Sep; 274(3):1042-53.JP

Abstract

We examined the pharmacological properties of U-97018, a novel nonpeptide angiotensin II (AII) receptor antagonist, in various in vitro and in vivo studies. U-97018 selectively displaced 125I-AII specific binding in the membrane fraction derived from the rat mesenteric artery and adrenal cortex (AT1 subtype) with IC50 of 1.3 +/- 0.2 and 7.7 +/- 1.3 nM, respectively, without altering the AII binding of the rat adrenal medulla (AT2 subtype). In rat adrenal cortical cells, U-97018 inhibited 1 nM AII-induced aldosterone secretion with an IC50 of 0.48 nM; it shifted concentration-secretion response curve for AII to the right and inhibited the maximal response to AII, yielding a pKB of 9.8. Similarly, U-97018 showed insurmountable antagonism with a pKB of 10.6 against the AII-induced contraction in the isolated rabbit aorta. U-97018 had no direct effect on the activities of renin and angiotensin converting enzyme in vitro. In pithed rats, U-97018 inhibited the AII-induced pressor response with an ED50 of 0.28 mg/kg, i.v. without any partial agonistic activity. In anesthetized rats and dogs, intraduodenal administration of U-97018 at a dose of 1 mg/kg inhibited the AII-induced pressor response by about 60%. In spontaneously hypertensive rats, U-97018 at 10 mg/kg p.o. produced antihypertensive effects which lasted for 24 hr after administration. Thus, U-97018 is an orally active, insurmountable AII receptor antagonist without any agonistic activity.

Authors+Show Affiliations

Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7562467

Citation

Kushida, H, et al. "Pharmacological Characterization of the Nonpeptide Angiotensin II Receptor Antagonist, U-97018." The Journal of Pharmacology and Experimental Therapeutics, vol. 274, no. 3, 1995, pp. 1042-53.
Kushida H, Nomura S, Morita O, et al. Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, U-97018. J Pharmacol Exp Ther. 1995;274(3):1042-53.
Kushida, H., Nomura, S., Morita, O., Harasawa, Y., Suzuki, M., Nakano, M., Ozawa, K., & Kunihara, M. (1995). Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, U-97018. The Journal of Pharmacology and Experimental Therapeutics, 274(3), 1042-53.
Kushida H, et al. Pharmacological Characterization of the Nonpeptide Angiotensin II Receptor Antagonist, U-97018. J Pharmacol Exp Ther. 1995;274(3):1042-53. PubMed PMID: 7562467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, U-97018. AU - Kushida,H, AU - Nomura,S, AU - Morita,O, AU - Harasawa,Y, AU - Suzuki,M, AU - Nakano,M, AU - Ozawa,K, AU - Kunihara,M, PY - 1995/9/1/pubmed PY - 1995/9/1/medline PY - 1995/9/1/entrez SP - 1042 EP - 53 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 274 IS - 3 N2 - We examined the pharmacological properties of U-97018, a novel nonpeptide angiotensin II (AII) receptor antagonist, in various in vitro and in vivo studies. U-97018 selectively displaced 125I-AII specific binding in the membrane fraction derived from the rat mesenteric artery and adrenal cortex (AT1 subtype) with IC50 of 1.3 +/- 0.2 and 7.7 +/- 1.3 nM, respectively, without altering the AII binding of the rat adrenal medulla (AT2 subtype). In rat adrenal cortical cells, U-97018 inhibited 1 nM AII-induced aldosterone secretion with an IC50 of 0.48 nM; it shifted concentration-secretion response curve for AII to the right and inhibited the maximal response to AII, yielding a pKB of 9.8. Similarly, U-97018 showed insurmountable antagonism with a pKB of 10.6 against the AII-induced contraction in the isolated rabbit aorta. U-97018 had no direct effect on the activities of renin and angiotensin converting enzyme in vitro. In pithed rats, U-97018 inhibited the AII-induced pressor response with an ED50 of 0.28 mg/kg, i.v. without any partial agonistic activity. In anesthetized rats and dogs, intraduodenal administration of U-97018 at a dose of 1 mg/kg inhibited the AII-induced pressor response by about 60%. In spontaneously hypertensive rats, U-97018 at 10 mg/kg p.o. produced antihypertensive effects which lasted for 24 hr after administration. Thus, U-97018 is an orally active, insurmountable AII receptor antagonist without any agonistic activity. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7562467/Pharmacological_characterization_of_the_nonpeptide_angiotensin_II_receptor_antagonist_U_97018_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7562467 DB - PRIME DP - Unbound Medicine ER -