In search of the mechanism of action of the nootropics: new insights and potential clinical implications.

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.