CLINICAL USES OF 2,3-DIMERCAPTOPROPANOL (BAL) .1. THE SYSTEMIC TREATMENT OF EXPERIMENTAL ARSENIC POISONING (MAPHARSEN, LEWISITE, PHENYL ARSENOXIDE) WITH BAL
CLINICAL USES OF 2,3-DIMERCAPTOPROPANOL (BAL) .1. THE SYSTEMIC TREATMENT OF EXPERIMENTAL ARSENIC POISONING (MAPHARSEN, LEWISITE, PHENYL ARSENOXIDE) WITH BAL
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DOI：
10.1172/jci101728
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发表时间：
1946-01-01
影响因子：
15.9
通讯作者：
FLEISCHMAN, R
中科院分区：
文献类型：
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作者：
EAGLE, H;MAGNUSON, HJ;FLEISCHMAN, R
BAL注射切口，肌肉内或静脉内。在水溶液或丙二醇溶液中，对家兔急性和亚急性马法生中毒有较好的治疗作用。BAL的解毒作用与其从与细胞结合的砷中清除砷的能力有关，并排出稳定且相对无毒的硫代亚砷酸盐。锥虫迅速固定，显然被砷剂杀死复苏的加入BAL，由于从细胞中去除的绑定As。同样地，在注射马法生、路易氏剂或苯基氧化砷的家兔中，admn。BAL引起尿砷排泄率的显著增加，在某些情况下超过100倍。虽然BAL在水溶液或丙二醇溶液中不稳定，solns。在花生油中，热杀菌的效果很好，但活性损失很小。加上2个GS。的苯甲酸苄酯。的BAL，后者是与花生油在所有比例混溶。毒性这类溶液的毒性在花生油和苯甲酸苄酯中，关于注射的频率和数量，管理的路线。，和浓度。的soln。BAL溶于花生油和苯甲酸苄酯肌肉注射。在治疗家兔的马法生、路易氏剂和苯基氧化砷中毒中证明有效。通过涉及4次注射的时间表提供了如此施用的BAL的有效水平和毒性水平之间的最宽安全范围。每隔2-4小时注射一次，在某些情况下随后每日注射。6天。在该方案中，1-10 mg/kg的个体BAL剂量。kg.保存接近。一半的动物注射了致死剂量的马法生、路易氏剂或苯基氧化砷。由于注射BAL的最大耐受剂量为35 mg。kg.，所提供的安全裕度足够大，表明其在人体使用的可行性。
BAL injected subcut., intramusc, or intraven. in aqueous or propylene glycol soln., proved effective in the treatment of acute and subacute mapharsen poisoning in rabbits. The antidotal action of BAL was referable to its ability to remove the arsenical from its combination with cells, with the excretion of the stable and relatively non-toxic thio-arsenite so formed. Trypanosomes rapidly immobilized and apparently killed by arsenicals were resuscitated on the addition of BAL, due to the removal of the bound As from the cell. Similarly, in rabbits injected with mapharsen, Lewisite, or phenyl arsenoxide, the admn. of BAL caused a striking increase in the rate of urinary As excretion, in some cases exceeding a 100-fold. Although BAL was unstable in aqueous or propylene glycol soln., solns. in peanut oil could be sterilized by heat with only slight loss in activity. With the addition of 2 gs. of benzyl benzoate for each g. of BAL, the latter was miscible with peanut oil in all proportions. The toxicity of such solns. in peanut oil and benzyl benzoate was detd. in relation to the frequency and number of injns., the route of admn., and the concn. of the soln. BAL dissolved in peanut oil and benzyl benzoate injected intramusc. proved effective in the treatment of mapharsen, Lewisite, and phenyl arsenoxide poisoning in rabbits. The widest margin of safety between the effective and toxic levels of BAL so administered was provided by a schedule involving 4 injns. at 2-4 hr. intervals, followed in some cases by daily injns. for 6 days. On this schedule, individual BAL doses of 1-10 mg./kg. saved approx. half the animals injected with lethal doses of mapharsen, Lewisite, or pheuyl arsenoxide. Since the maximum tolerated dose of BAL so injected was 35 mg./kg., the margin of safety provided was sufficiently large to indicate the feasibility of its human use.