Safety Pharmacology of CJ-11555

Safety pharmacological properties of CJ-11555, an anti-cirrhotic agent, were investigated in experimental animals and in vitro test system. CJ-11555 had no effects on normal body temperature in rats, motor coordination, chemoshock induced by pentetrazol, electric shock induced by electric shocker and writhing syndromes in mice at dose levels of 100, 300 and 1,000 mg/kg. CJ-11555 inhibited intestinal activity and prolonged hexobarbital-induced sleeping time in mice at the dose level of 1,000 mg/kg. CJ-11555 affected on general activity and behaviour tests in SD rats, such as lacrimation, ptosis, piloerection, decreased body tone, abnormal dispersion within the cage, diarrhoea, red colored faeces, slight hypothermia and decreased grooming, at the dose level of 1,000 mg/kg in rats. CJ-11555 was effected on cardiovascular and respiratory system in anesthetized beagle dogs, such as tachycardia, increase of mean blood pressure and decrease of PR interval, decrease of respiratory rate and minute volume, at dose levels of 10 and 30 mg/kg. However, these effects were also observed in vehicle treated anesthetized beagle dogs. In in vitro experiments, CJ-11555 inhibited agonists (histamine, acetyl-choline or $BaCl_2$) induced contraction of isolated guinea-pig at the concentration of 30$\times$$10^6$ M. CJ-11555 was weekly inhibited hERG channel current at concentrations of 10 and 30$\times$$10^6$ M, and $IC_{50}$ was estimated to be higher than 30${\times}$$10^6$M. Based on these results, it was concluded that CJ-11555 affected on cardiovascular and respiratory system, general activity and behaviour and hexobarbital-induced sleeping time at the dose level of 1,000 mg/kg and contraction of the smooth muscle and hERG channel current at the concentration of 30$\times$$10^6$ M.

CJ-11555의 안전성 약리실험