Rodatristat ethyl (KAR5585) is a first-of-its-kind orally active and potent tryptophan hydroxylase 1 (TPH1) inhibitor that significantly reduces 5-hydroxytryptamine (5-HT) levels and decreases pulmonary arterial hypertension (PAH) at low concentrations.

In male Sprague-Dawley rats, oral administration of rodatristat ethyl at doses of 100 or 200 mg/kg once daily for 28 days results in a dose-dependent decrease in serum, gut, and lung 5-HT levels. This treatment significantly reduces pulmonary arterial pressure as well as pulmonary vessel wall thickness and occlusion in rats with monocrotaline (MCT)-induced pulmonary hypertension[2].