Brain Food: Piracetam II
From David Tolson's article
http://www.bulknutri...m/?articleID=87
Glutamate
The glutamatergic system is the only receptor system which piracetam seems to have a direct effect on [1, 8, 15]. Piracetam binds to some glutamate receptors, although this may not be at all relevant in normal doses [1]. Despite this, one review contends that the glutamatergic system may play a central role in piracetam's nootropic activity [1].
One of the main supporting pieces of evidence for this hypothesis is that the memory-enhancing effects of piracetam can be easily blocked by NMDA channel blockers. Both ketamine and MK-801 antagonize the nootropic effect. In a Russian study, it was found that piracetam potentiated the response to glutamate and aspartate through the glycine site of the NMDA receptor, and this effect may be obscured by the presence of glycine. This would indicate a direct effect at the glycine site, and another 2-pyrrolidinone derivative, HA-966, exhibits antagonistic properties at the glycine site [1]. Again, this effect has not been demonstrated to be relevant in normal doses. Piracetam also prevents the age-related decrease in NMDA receptor density [16], but this could easily be due to nonspecific action.
Piracetam may also have important effects on AMPA receptors. As is the case with NMDA receptors, it increases the density of AMPA receptor sites [1, 16]. More importantly, piracetam increases the efficiency, but not potency, of AMPA-induced calcium influx and antagonizes the effect of the L-type calcium channel blocker nifedipine. This represents a promising and largely unexplored mode of action, since positive modulation of AMPA receptors is also an effect shared by other cognition enhancers such as the ampakines and aniracetam.
1: Child Psychiatry Hum Dev. 2008 Sep;39(3):237-45. Epub 2007 Oct 11.
Links A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder.
Akhondzadeh S, Tajdar H, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Shabstari OL, Ghelichnia HA. Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran. s.akhond@neda.net
It has been reported that autism is a hypoglutamatergic disorder. Therefore, it was of interest to assess the efficacy of piracetam, a positive modulator of AMPA-sensitive glutamate receptors in autistic disorder. About 40 children between the ages three and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to piracetam + risperidone (Group A) or placebo + risperidone (Group B) for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of piracetam was titrated up to 800 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale (total score). The ABC-C Rating Scale scores improved with piracetam. The difference between the two protocols was significant as indicated by the effect of group, the between subjects factor (F = 5.85, d.f. = 1, P = 0.02). The changes at the endpoint compared with baseline were: -11.90 +/- 3.79 (mean +/- SD) and -5.15 +/- 3.04 for group A and B respectively. A significant difference was observed on the change in scores in the ABC-C Rating Scale in week 10 compared with baseline in the two groups (t = 6.017, d.f. = 38, P < 0.0001). The results suggest that a combination of atypical antipsychotic medications and a glutamate agent such as piracetam, might have increase synergistic effects in the treatment of autism.
Edited by Rags847, 25 July 2008 - 12:51 AM.
