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Survey of Dopamine Receptor D2 Antagonists as Retinal Antifibrotics.
- Source :
-
Journal of Ocular Pharmacology & Therapeutics . Oct2024, Vol. 40 Issue 8, p536-542. 7p. - Publication Year :
- 2024
-
Abstract
- Purpose: To evaluate the potency and efficacy of a library of dopamine receptor D2 (D2R) antagonists in the mitigation of fibrotic activation in retinal pigment epithelial (RPE) cells. Methods: ARPE-19 cells were cultured and treated with methotrexate or 27 district D2R antagonists using a fibronectin deposition assay. The most potent compounds were then further assessed in assays measuring cellular proliferation, cellular migration, and profibrotic gene expression. Results: The previously established antifibrotic D2R antagonist loxapine exerted a robust and dose-dependent inhibition of fibronectin deposition, whereas methotrexate exerted minimal inhibition. The most potent D2R antagonist identified, fluphenazine, effectively blocked in vitro models of fibrosis at 300–1,000 nM concentrations. Conclusions: Here we found multiple FDA-approved D2R antagonists that potently block RPE cell fibrogenesis. These findings further support the potential of D2R antagonism as a potential therapeutic for retinal fibrotic disease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10807683
- Volume :
- 40
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Ocular Pharmacology & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 180328273
- Full Text :
- https://doi.org/10.1089/jop.2024.0006