Avosentan(Ro 67-0565; SPP-301) is a potent endothelin receptor (ETA) antagonist with strong inhibitory effects on endothelin-1-induced contraction and may have protective effects against chronic kidney disease. [2]

ETA:3 nM

METHODS: Avosentan (Ro 67-0565; SPP-301) was administered by intragastric administration in a single dose (6 rats per group: 0.1, 1.0, 10, 100 mg/kg). Rats were placed in metabolic cages for 24 hours after administration to assess body fluid electrolyte homeostasis.
RESULTS The highest dose (100 mg/kg) of Avosentan (Ro 67-0565; SPP-301) resulted in reduced 24-hour diuresis (18.3%) and natriuresis (17.6%), hematocrit, and hematocrit in a hypertensive dTGR model Then it dropped. [1]
METHODS: Apolipoprotein E (Apoe) knockout (KO) mice were randomly assigned to the following groups: nondiabetic controls and streptozotocin-induced diabetic animals treated daily with placebo, Avosentan (Ro 67-0565; SPP -301) (high dose: 30 mg/kg, or low dose: 10 mg/kg) by intragastric administration for 20 weeks.
RESULTS Blood pressure remained unchanged after Avosentan (Ro 67-0565; SPP-301) treatment. High-dose Avosentan (Ro 67-0565; SPP-301) could significantly reduce diabetes-related albuminuria after 10 and 20 weeks of treatment. Creatinine clearance was normalized with Avosentan (Ro 67-0565; SPP-301). In diabetic mice, high-dose Avosentan (Ro 67-0565; SPP-301) treatment significantly attenuated the glomerulosclerosis index, mesangial matrix accumulation, glomerular accumulation of the matrix protein collagen IV, and the encoded connective tissue growth factor , renal expression of genes for vascular endothelial growth factor, transforming growth factor beta, and nuclear factor kappa B (p65 subunit). [2]