Mondadori C
CIBA-GEIGY LTD, Pharmaceutical Research Division, Basel, Switzerland.
Life Sci. 1994;55(25-26):2171-8. doi: 10.1016/0024-3205(94)00398-x.
The positive action of nootropics on the memory has up to now primarily been discussed in the context of effects on energy metabolism and cholinergic or glutaminergic neurotransmission. Recent findings have shown that the memory-enhancing effect is steroid-sensitive. Since corticosteroids are potent modulators of gene transcription, it appears possible that the nootropics may exert a modulatory action on protein synthesis. This assumption is supported on the one hand by the fact that the nootropics improve the memory even if they are administered several hours after the learning trial, and on the other hand by the observation that their memory-enhancing effect does not become detectable until 16-24 hours after the treatment and learning trial. Provided the memory-enhancing effect in animal experiments and the therapeutic effect in patients come about by way of the same mode of action, the fact that high levels of corticosteroids suppress the effects of the nootropics could also have clinical implications: in the light of the observation that the majority of Alzheimer patients have elevated steroid levels it could explain why there is always only a small proportion of patients in clinical trials that respond to treatment with nootropics.
到目前为止，益智药对记忆的积极作用主要是在其对能量代谢以及胆碱能或谷氨酸能神经传递的影响背景下进行讨论的。最近的研究结果表明，记忆增强作用对类固醇敏感。由于皮质类固醇是基因转录的有效调节剂，因此益智药可能对蛋白质合成发挥调节作用。这一假设一方面得到以下事实的支持：即使在学习试验数小时后给药，益智药仍能改善记忆；另一方面也得到以下观察结果的支持：其记忆增强作用直到治疗和学习试验后的16 - 24小时才会显现出来。假设在动物实验中的记忆增强作用和在患者中的治疗作用是通过相同的作用方式实现的，那么高水平的皮质类固醇会抑制益智药的作用这一事实也可能具有临床意义：鉴于观察到大多数阿尔茨海默病患者的类固醇水平升高，这可以解释为什么在临床试验中总是只有一小部分患者对益智药治疗有反应。
