Safety Pharmacology
Safety Pharmacology
Central nervous system
- General physical condition and behavior (modified Irwin's method: mice, rats / FOB method: rats, cynomolgus monkeys, beagles)
- Locomotor activity (mice, rats)
- Body temperature (rats / telemetry method: cynomolgus monkeys, rhesus monkeys, beagles, common marmosets)
Cardiovascular system
In Vivo
Blood pressure*, heart rate, influence on the electrocardiogram* under conscious and unrestrained conditions
(Telemetry method: cynomolgus monkeys, rhesus monkeys, beagles, common marmosets)
*: Left ventricular pressure and epicardial electrocardiogram is available in cynomolgus monkeys, rhesus monkeys, and beagles
In Vitro
Effect on the potassium current (hERG current)
（whole-cell patch clamp method: hERG transfected CHO or HEK293 cells）
- Effect on the action potential
(Microelectrode method: guinea pig papillary muscle) - Effect on the L-type calcium current (ICa, L)
(Whole-cell patch clamp method: guinea pig left ventricular myocytes)
Respiratory system
- Respiratory rate (telemetry method: conscious cynomolgus and rhesus monkey) and blood gas analysis (pH, PO2, PCO2, and SPO2)
- Respiratory rate, tidal volume, and minute volume
(Whole Body Plethysmograph method: conscious rats)
Gastrointestinal system
- Small intestinal transport capacity (mice, rats)
- Gastric emptying capacity (rats)
Renal / urinary system
- Effects on water and electrolyte metabolism (rats)