Shiu G K, Nemoto E M, Nemmer J
Crit Care Med. 1983 Jun;11(6):452-9. doi: 10.1097/00003246-198306000-00013.
Recent interest in pharmacotherapy for various cerebral insults with potentially dangerous drugs, such as barbiturate anesthetics, has created a need to determine the lowest or optimal dose resulting in maximal therapeutic effects. Our earlier studies suggested that whole brain free fatty acid (FFA) accumulation during complete global ischemia reflects the evolution of brain damage. Various drugs effective in ameliorating ischemic brain injury were also effective in attenuating FFA accumulation. The degree of attenuation by a given drug at various doses may indicate the optimal dose. We studied the attenuation of whole brain FFAs (i.e., 20:4, 18:0, 18:1, and 16:0) by 15-120 mg/kg of thiopental or pentobarbital, or 50-300 mg/kg of phenytoin or ketamine intraperitoneal (IP), during 10-min decapitation ischemia in rats. Plasma and brain drug levels were measured except ketamine. Maximal attenuation of FFAs occurred at pentobarbital, thiopental, and phenytoin doses of 15, 30, and 150 mg/kg IP reducing total FFA by 18, 22, and 31%, respectively. These results indicate that maximal therapeutic effects are obtained at subanesthetic doses of barbiturates and at the anticonvulsant dose of phenytoin.
近期，使用诸如巴比妥类麻醉剂等具有潜在危险性的药物对各种脑损伤进行药物治疗引发了人们的关注，这就需要确定能产生最大治疗效果的最低或最佳剂量。我们早期的研究表明，全脑在完全性全脑缺血期间游离脂肪酸（FFA）的蓄积反映了脑损伤的发展过程。各种有效减轻缺血性脑损伤的药物在减轻FFA蓄积方面也同样有效。给定药物在不同剂量下的减轻程度可能表明最佳剂量。我们研究了在大鼠断头缺血10分钟期间，腹腔注射（IP）15 - 120mg/kg硫喷妥钠或戊巴比妥，或50 - 300mg/kg苯妥英或氯胺酮对全脑FFA（即20:4、18:0、18:1和16:0）的减轻作用。除氯胺酮外，还测量了血浆和脑内药物水平。戊巴比妥、硫喷妥钠和苯妥英腹腔注射剂量分别为15、30和150mg/kg时，FFA的最大减轻程度分别为18%、22%和31%。这些结果表明，巴比妥类药物的亚麻醉剂量和苯妥英的抗惊厥剂量可获得最大治疗效果。
