The Clinically-tested S1P Receptor Agonists, FTY720 and BAF312, Demonstrate Subtype-Specific Bradycardia (S1P1) and Hypertension (S1P3) in Rat
Figure 5
Effect of FTY720 and BAF312 on mean arterial pressure (MAP) and heart rate (HR) in conscious, telemetry-instrumented, rats during 10 days of daily oral administration.
At doses that elicited no significant bradycardia, FTY720 elicited dose-dependent hypertension whereas BAF312 had no affect on MAP values at any dose tested during the study. FTY720 elicited dose-dependent increases in MAP at all doses tested (0.5, 1.5, and 5.0 mg/kg/d); 24-hr mean values over the treatment period increased 8.4±0.4, 12.8±0.4, and 16.2±0.8 mmHg, respectively, (vehicle = 3.7±0.5 mmHg) and values reached statistical significance in all treated groups (*p<0.05 vs. vehicle). However, BAF312 elicited no significant increase in mean arterial pressure during the study; average changes in 24-mean values during 14-days of treatment in the 0.3, 3.0, and 30 mg/kg/d dose groups were 3.0±0.5, 1.1±0.5, and 0.1±0.5 mmHg, respectively.