Actually i'm more focused in schizophrenia research issues,i considere that his caracteristic implication of glutamate deficience system is actually one of the more important target in nootropic strategy.
We know quite well the nootropics issues derived from alzheimer,parkinson,depression investigacion (acetylcholine,dopamine and serotonin precursors, IMAO's etc etc...) but the comprehension of the shizophrenia mechanisms and his potential nootropic treament have been subestimed or simply unknows in the comunity.Simplifying,the disease is characterized by "positive symptoms"result of the D2 receptor overactivity in ganglio basal (mesolimbic) on the one hand and a hypometabolism in the rest of cortex particulary in D1 prefrontal receptors (negative symptoms).Negative symptoms are principaly vinculed with deficience in comunications capacity,poor creativity in speech ,linguistic cognition in general,working memory and a subtyp of depression/apaty lack of motivation , consequently social and affective retraction.

Until recently shizophrenia treatment was focused to control positive symptoms with D2 antagonists ( typical antipsychotics) wich not improve cognitive syptoms and any atypicals with sligt improvement.More recently glutamate hypofunction has been implicated in the dopamine mesolimbic/mesocortex unbalance ,NMDA circuit modulate dopamine neurons
inhibiting D2 activity though dopamine mesolimbic pathway and "activing" the projection of corical pyramidal neurons to dopamines neurons in prefrontal cortex from the tegmental area.
Then that is the point,NMDA agonists and coagonists are under investigacion(some of then in phase 3),they have show to be effective,specially for improve negative/cognitive symptoms .NMDA coagonists seems tu be particulary interesants ,they don't show to have a risk of exitotoxicity like direct agonists (maybe taurine or magnesium could help in this case?)Further this strategy could be more effective in comparison to simply take dopamine precursors or IMAO to release dopamine.
Besides that,AMPAkines have show to be effective and are in investigacion too and also is being considered neurotrofic treatments for HPA but is another story...

Treatment issues for shizophrenia cognitive symptoms could be very interesants to our purposes.

I know my english is pathetic LOL but nobody is curious about this subject?? wowww



Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia.

Noorbala AA, Akhondzadeh S, Davari-Ashtiani R, Amini-Nooshabadi H.

Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.

OBJECTIVE: There is a growing interest in investigating the role of glutamate receptors in the pathophysiology of schizophrenia. Indeed, the hyperdopaminergic theory of schizophrenia can explain only the positive symptoms of schizophrenia, whereas the glutamate hypothesis may provide a more comprehensive view of the illness. We undertook a trial to investigate whether the combination of haloperidol with piracetam, a nootropic agent which modulates the glutamate receptor positively was more effective than haloperidol alone. METHODS: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 14 to haloperidol 30 mg/day plus piracetam 3200 mg/day and 16 to haloperidol 30 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the score of the positive symptoms, the negative symptoms, the general psychopathological symptoms and the total score of PANSS scale over the trial period, the combination of haloperidol and piracetam showed a significant superiority over haloperidol alone in the treatment of schizophrenic patients. CONCLUSION: Piracetam, a member of the nootropic class of drugs and a positive modulator of glutamate receptor, may be of therapeutic benefit in treating schizophrenic patients in combination with typical neuroleptics. However, a larger study to confirm our results is warranted.

PMID: 10583700 [PubMed - indexed for MEDLINE]




Long-term potentiation depends on release of D-serine from astrocytes.

Henneberger C, Papouin T, Oliet SH, Rusakov DA.

UCL Institute of Neurology, University College London, London WC1N 3BG, UK.

Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory. The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has been shown that astroglia can regulate their activation through Ca(2+)-dependent release of the NMDAR co-agonist D-serine. Release of D-serine from glia enables LTP in cultures and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus. However, increases in Ca(2+) concentration in astroglia can also release other signalling molecules, most prominently glutamate, ATP and tumour necrosis factor-alpha, whereas neurons themselves can synthesize and supply D-serine. Furthermore, loading an astrocyte with exogenous Ca(2+) buffers does not suppress LTP in hippocampal area CA1 (refs 14-16), and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned. The involvement of glia in LTP induction therefore remains controversial. Here we show that clamping internal Ca(2+) in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine, whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We therefore demonstrate that Ca(2+)-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby.

PMID: 20075918 [PubMed - in process]






D-Serine and a glycine transporter inhibitor Sarcosine improve MK-801-induced cognitive deficits in a novel object recognition test in rats.

Karasawa J, Hashimoto K, Chaki S.

Discovery Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5 mg/kg, i.p.) but not haloperidol (0.03, 0.1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with D-serine at 800 mg/kg (i.p.) or NFPS (0.3, 1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

PMID: 17854919 [PubMed - indexed for MEDLINE]

This post has been edited by gwen: Feb 8 2010, 05:20 PM

Well, there are various types of schizophrenia, requiring different treatments. I'm no expert on this subject, but having talked to a few doctors, they all say that they never prescribe Piracetam without tranquilizers, and mostly go with antidepressants, antipsychotics, or benzos to hold off any potential psychostimulant effects of noots. 

Around here though, they love to load you up full of sedatives, because they don't trust you with your newly acquired mental faculties  

Pantogam (hopatenic acid) is used in treatments of certain types of scizophrenia, with or without antidepressants, according to the instruction manual.




That's about all I can add.

The last thing that someone with schizophrenia needs is a psychostimulant.

There's what they call "scizophernia with prevailing apathy and loss of motivation" so they prescribe some noots (Pantogam) for that exact cause. The instruction manual still suggests to use it with antidepressants and tranquilizers.

All noots are psychostimulants, so they're just trying to tread carefully.




Those with more agressive forms of scizophrenia shuold probably also stay away from benzos as well, although doctors have no problem prescribing them for life...a good way to go even more nuts...

[

Psychostimulants are not a problem in schizophrenia provided that they no implicate any mechanism in relation with D2r agonism what could exacerbate psychotic symptoms.In fact,Modafinil for example is used for cognitive symptoms treatment without any "tranquilizers".

russianBEAR i think you mean psychoactiv when you say all noots are psychostimulants ,right?

Besides that,the basic idea would further the potential of NMDA agonism strategy for cognitive symptoms.


PS:Any misunderstanding is sponsored by Google traductor

No, I mean psychostimulants...psychoactive could imply a variety of effects, even those that aren't stimulating per se...alcohol for instance is psychoactive...Every nootropic's instruction manual says they have "psychostimulating" properties. Meaning they stimulate just the brain...amphetamines are more central nervous system stimulants...all of that is intertwined but I guess it's about the mechanism of action.


It's very likely though that I dunno the corresponding term in English for this...

Around here though they'd rather just subdue you to the point of total vegetation if you got schizophrenia...they'd rather not take a risk on you "healing" then being out in public...so they just kill you basically with sedatives...

Go ad free, join ImmInst as a Full Member.