Description: |
SHR-1977 (ROMK IC50 = 44 nM, hERG IC50 = >100,000 nM) displayed a linear exposure relationship with dose in rats and dogs. SHR-1977 also showed selectivity for ROMK over other inward-rectifier potassium ion channels. In rats, diuresis and natriuresis were increased with oral doses of 0.3 mg/kg (3.88- and 3.25-fold, respectively, compared to vehicle) and 1.0 mg/kg (4.77- and 2.92-fold, respectively, compared to vehicle). In spontaneously hypertensive rats, daily mean systolic blood pressure was significantly reduced by these doses given for 3 days. |