2. Academic Validation
  3. First reported nonpeptide AT1 receptor agonist (L-162,313) acts as an AT2 receptor agonist in vivo

First reported nonpeptide AT1 receptor agonist (L-162,313) acts as an AT2 receptor agonist in vivo

  • J Med Chem. 2004 Mar 11;47(6):1536-46. doi: 10.1021/jm031031i.
Yiqian Wan 1,  Charlotta Wallinder,  Berndt Johansson,  Mathias Holm,  A K Mahalingam,  Xiongyu Wu,  Milad Botros,  Anders Karlén,  Anders Pettersson,  Fred Nyberg,  Lars Fändriks,  Anders Hallberg,  Mathias Alterman
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden. mathias.alterman@orgfarm.uu.se
PMID: 14998339 DOI: 10.1021/jm031031i
Abstract

In this investigation, it is demonstrated that the first nonpeptide AT(1) receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT(2) receptor. In anesthetized rats, administration of compound 1 intravenously or locally in the duodenum increased duodenal mucosal alkaline secretion, effects that were sensitive to the selective AT(2) receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT(2) receptor agonist in vivo. To the best of our knowledge, this substance is the first nonpeptidic low-molecular weight compound with an agonistic effect mediated through the AT(2) receptor.

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