Vasin M V, Chernov G A, Antipov V V
State Scientific Research Testing Institute of Aviation and Space medicine MD of the Russian Federation, Moscow.
Radiats Biol Radioecol. 1997 Nov-Dec;37(6):896-904.
In the experiments on mice, rats, hamsters, guinea pigs, dogs and Macaca Rhesus ED50, the width of radioprotective effect of indralin from alpha-adrenomimetics was investigated. It was made an estimate by ED50, LD50 and therapeutic index (TI): ED50/LD50. ED50 of indralin i.m. on mice is 21.9 (16.2-29.4) mg/kg, on guinea pigs --28.8 (17.0-49.0) mg/kg, on hamsters --50.7 (42.9-59.8) mg/kg and on dogs --6.0 (4.3-8.3) mg/kg. TI of indralin i.m. for same animals is correspondingly equal to 23.7 (15.3-36.5), 25.6 (13.7-47.4), 17.8 (14.8-24.1) and 31.1 (20.6-47.3). TI of indralin p.o. for rats and dogs is close to 18.2 and 23.7. Under the equal conditions TI of cystamine for mice, rats (i.p.) and dogs (i.v.) is respectively 3.3 (2.82-3.70), 2.1 (1.57-2.82) and 1.22. T50 of the elimination of indralin on mice (100 mg/kg i.p. and i.m.) for toxicologic properties measured circa 5-10 min. Under the conditions of repeated application in 30-60 min indralin desensitization to toxic doses happened as the rise of LD50 by 15-30%. T50 of the elimination of indralin in optimum doses for the pharmacodynamic of radioprotective effect is 19.3 (13.3-28.0) min on mice, --19.2 (15.3-25.9) on hamsters, --26.9 (20.4-35.5) on rats and --40.2 (30.5-53.1) min on dogs. In the transition from the experiment on mice to dogs twofold rise of T50 of the elimination of indralin doesn't combine with adequate increase the toxicity of the radioprotector. Pathophysiologic foundation of distinctions between aminothiols and radioprotector realizing the effect through cell receptor in the width of radioprotective effect is discussed.
在对小鼠、大鼠、仓鼠、豚鼠、狗和恒河猴进行的实验中，研究了因得拉林相对于α-肾上腺素能药物的辐射防护作用宽度。通过半数有效剂量（ED50）、半数致死剂量（LD50）和治疗指数（TI）即ED50/LD50进行评估。因得拉林腹腔注射对小鼠的ED50为21.9（16.2 - 29.4）mg/kg，对豚鼠为28.8（17.0 - 49.0）mg/kg，对仓鼠为50.7（42.9 - 59.8）mg/kg，对狗为6.0（4.3 - 8.3）mg/kg。因得拉林腹腔注射对相同动物的TI分别为23.7（15.3 - 36.5）、25.6（13.7 - 47.4）、17.8（14.8 - 24.1）和31.1（20.6 - 47.3）。因得拉林口服对大鼠和狗的TI接近18.2和23.7。在相同条件下，胱胺对小鼠、大鼠（腹腔注射）和狗（静脉注射）的TI分别为3.3（2.82 - 3.70）、2.1（1.57 - 2.82）和1.22。就毒理学特性而言，腹腔注射和肌肉注射100 mg/kg因得拉林后，小鼠体内因得拉林消除的T50约为5 - 10分钟。在30 - 60分钟内重复给药的条件下，因得拉林对毒性剂量出现脱敏现象，LD50升高了15 - 30%。就辐射防护作用的药效动力学而言，因得拉林在最佳剂量下消除的T50，对小鼠为19.3（13.3 - 28.0）分钟，对仓鼠为19.2（15.3 - 25.9）分钟，对大鼠为26.9（20.4 - 35.5）分钟，对狗为40.2（30.5 - 53.1）分钟。在从对小鼠实验过渡到对狗的实验过程中，因得拉林消除的T50增加了两倍，但辐射防护剂的毒性并未相应增加。文中讨论了氨基硫醇和通过细胞受体发挥作用的辐射防护剂在辐射防护作用宽度方面存在差异的病理生理基础。
