Lahti R A, Barsuhn C
Res Commun Chem Pathol Pharmacol. 1975 Aug;11(4):595-603.
Minor tranquilizers have been shown to be specific inhibitors of the elevation of plasma corticosteroid levels in rats subjected to mild stress. The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range. It was found that at high doses, the drugs themselves cause an elevation of corticosteroid levels masking the blocking of the stress-induced elevations. It was discovered that upon sub-chronic administration, the drug-induced elevation diminishes while the ability to inhibit stress-induced elevation persists. Finally, an extensive dose response curve for phenobarbital demonstrated a variety of responses, depending upon the dose; an antistress effect at low dose, a relatively ineffective dose range from 50-100 mg/kg, and a corticosteroid lowering effect at anesthetic doses. The lack of effect of moderately high doses has been explained through their depressant side effects, which in themselves are stressful to the animal.
已证明，小剂量镇静剂是轻度应激大鼠血浆皮质类固醇水平升高的特异性抑制剂。几种抗焦虑化合物在高剂量时无活性，这促使人们对这些药物在更广泛剂量范围内对皮质类固醇水平的影响进行研究。结果发现，在高剂量时，药物本身会导致皮质类固醇水平升高，从而掩盖了对应激诱导升高的阻断作用。研究发现，亚慢性给药后，药物诱导的升高作用减弱，而抑制应激诱导升高的能力持续存在。最后，苯巴比妥的广泛剂量反应曲线显示出多种反应，这取决于剂量；低剂量时有抗应激作用，50-100mg/kg的剂量范围相对无效，麻醉剂量时有皮质类固醇降低作用。中等高剂量无效已通过其抑制性副作用来解释，这些副作用本身对动物就是一种应激。
