General Pharmacology of Erythropoietin Produced by a New Recombinant DNA Technique

새로운 유전자 재조합 기술에 의하여 생산된 Erythropoietin의 일반약리작용

The general pharmacological properties of EPO were investigated in various animals administering intravenously and in vitro system. The results were as follows. 1. Central nervous system: EPO at doses of 70, 700, 7000 U/kg showed no effect In mice on general behavior, on strychnine- and pentetrazol-induced convulsion and on acetic acid-induced writhing syndrome. The hexobarbital-induced sleeping time in mice was slightly reduced by EPO at a dose of 7000 U/kg but did not change at doses of 70, 700 U/kg. The body temperature in rats was slightly decreased by EPO at doses of 700, 7,000 U/kg but the change was in normal physiological range. 2. Respiratory and cardiovascular system: EPO showed no effect on respiratory rate, blood pressure, heart rate, femoral blood flow, and electrocardiogram in anesthetized dogs at doses of 70, 700, 7000 U/kg. 3. Smooth muscle: EPO at concentrations of 70, 700 U/ml had no effect on the contractile response of isolated guinea pig ileum to histamine and acetylcholine. 4. Water and electrolytes excretion: EPO at dose above 700 U/kg increased urine volume in rats but did not affect the concentrations of $Na^{+},\;K^{+},\;Cl^{-}$ in urine. 5. Gastrointestinal system: EPO(70, 700, 7000 U/kg) had no effect on the intestinal charcoal meal propulsion 6. Blood coagulation system: The administration of EPO(70, 700, 7000 U/kg) had no effect on the plasma prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice. Platelet aggregation induced by ADP and collagen was not influenced by EPO(70 U/ml, 700 U/ml). The overall results obtained indicated that EPO exerts almost no serious pharmacological effect even at a 100-fold clinical dose(7000 U/kg).