A peripherally restricted P2Y₁₂ receptor antagonist altered rat tumor incidences with no human relevance: Mode of action consistent with dopamine agonism.

ABSTRACT:

Background

Ticagrelor is an orally available, direct acting and reversible P2Y₁₂ receptor antagonist approved for treatment of acute coronary syndrome. The objectives of these studies were to (1) evaluate the Ticagrelor 2-year rat carcinogenicity bioassay data; (2) investigate potential mode of action (MOA) and (3) interpret human relevance.

Methods

The following studies were done (1) rat two-year carcinogenicity study in male and female rats, (2) in vitro and in vivo genotoxicity assays, (3) quantitative whole body autoradiography (QWBA; male and female rats), (4) in vitro pharmacological profiling for more than 300 assays, and (5) in vivo ovariectomized rat assay.

Results

The carcinogenicity study indicated Ticagrelor increased

SUBMITTER: Brott DA 

PROVIDER: S-EPMC5598522 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature