%A Bhat, Laxminarayan %A Bhat, Seema R %A Nault, Marie-Claude %A Biernat, Marzena %A Labbe, Sebastien M %D 2023 %T Evaluation of Brilaroxazine (RP5063) in a Bleomycin-Induced Rodent Model of Idiopathic Pulmonary Fibrosis %K %X Idiopathic pulmonary fibrosis pathology involves serotonin (5-HT), with an increased expression of 5-HT 2A/2B/7 receptors in the lungs. This study tests the hypothesis that brilaroxazine (RP5063), an agent with a potent binding affinity for serotonin 5-HT 1A/2A/2B/7 and dopamine D 2/3/4 receptors , and moderate affinity for the 5-HT transporter, dosed at 15 mg twice daily (b.i.d.) shows efficacy as compared with placebo in a bleomycin (BLM)-induced model using Sprague Dawley rats. On Day 0, four groups received BLM-induction, and one received placebo. On Day 1, one group started on brilaroxazine (RPT). On Day 10, two groups started on brilaroxazine (RPI) and one continued on the vehicle (BLM). All interventions continued until Day 20.  Compared with BLM, RPT and RPI sustained survival at 90.5% and 89.5%, respectively ( P <0.05) and maintained weight ( P <0.01). RPT normalized pulse pressure and cardiac output. It also lowered respiratory resistance, hydroxyproline, lung weight, bronchoalveolar lavage fluid cell counts, and total protein ( P <0.05). RPI decreased hydroxyproline and reduced cell counts ( P <0.01). Brilaroxazine lowered Ashcroft scores and Masson’s Trichome staining ( P <0.001).  Both brilaroxazine groups reduced proinflammatory and fibrotic cytokines ( P <0.05). Brilaroxazine attenuated BLM-induced pulmonary fibrosis, inflammation, and extracellular deposition and improved cardiac and pulmonary functions in rodents.   %U https://esmed.org/MRA/mra/article/view/3837 %J Medical Research Archives %0 Journal Article %R 10.18103/mra.v11i4.3837 %V 11 %N 4 %@ 2375-1924 %8 2023-05-25