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)


hERG transfected CHO cells
hERG transfected CHO cells
hERG transfected HEK293 cells
hERG transfected 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)
Guinea pig left ventricular myocytes
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)