These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: In vivo pharmacological characterization of UP 269-6, a novel nonpeptide angiotensin II receptor antagonist.
    Author: Cazes M, Provost D, Versigny A, Cloarec A.
    Journal: Eur J Pharmacol; 1995 Sep 15; 284(1-2):157-70. PubMed ID: 8549620.
    Abstract:
    UP 269-6, 5-methyl-7-propyl-8(-)[2'-(1H-tetrazol-5-yl)biphenyl-4- yl)methyl]-1,2,4-triazolo]1,5-c]pyrimidin-2(3H)-one is a novel nonpeptide angiotensin II receptor antagonist. In vivo studies were performed to evaluate UP 269-6 for its angiotensin II antagonistic action. In pithed rats, i.v. administration of UP 269-6 (0.03-1 mg/kg) shifted dose dependently to the right the dose-pressor response curve for angiotensin II and decreased the maximum response. The angiotensin II antagonistic effect of UP 269-6 was as potent as that of L-158,809 (5,7-dimethyl-2-ethyl-3(-)[[2'- (1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazo[4,5-b]pyridine) and 10 times more potent than that of losartan. UP 269-6 antagonized the angiotensin II sympathetic-mediated tachycardiac response. UP 269-6 inhibited dose dependently the pressor response to angiotensin II with an ID50 of 4.5 micrograms/kg, i.v. in conscious normotensive dogs. Oral administration of UP 269-6 (0.1 to 30 mg/kg) resulted in a dose-dependent and long-lasting inhibition of the angiotensin II-induced pressor response in conscious normotensive rats and dogs. Compared to losartan, UP 269-6 presented a more rapid onset of action. UP 269-6 caused similar angiotensin II antagonistic effects in rats and dogs but the duration of the effect was greater in dogs than in rats. UP 269-6 did not alter the tachycardiac response to isoproterenol and the pressor response to vasopressin. UP 269-6 was demonstrated to be devoid of agonistic properties in rats and dogs. Furthermore, UP 269-6 did not induce hypotension and did not cause alteration in heart rate and ECG waveforms in dogs even at a dose 1000 times higher than the angiotensin II antagonistic effective dose. These results demonstrate that UP 269-6 is a potent and specific angiotensin II receptor antagonist and dose not possess agonistic properties.
    [Abstract] [Full Text] [Related] [New Search]