Why do you want to avoid NO (assuming you mean Nitric Oxide)?
Current research shows that NO might have benfical or detrimental effects on the brain.
I don't want to mess with it, therefore.
Here is the article on Pramiracetam and NO.
http://www.biopsychi...amiracetam.html
Systemic administration of pramiracetam increases
nitric oxide synthase activity in the cerebral cortex of the rat
by
Corasaniti MT, Paoletti AM, Palma E,
Granato T, Navarra M, Nistico G.
Faculty of Pharmacy,
University of Reggio Calabria,
Catanzaro, Italy.
Funct Neurol 1995 May-Jun;10(3):151-5
ABSTRACT
The effect of systemic administration of pramiracetam on neuronal type nitric oxide synthase (NOS) activity and NOS mRNA expression were studied in the hippocampus and cerebral cortex in rats. A dose of 300 mg/kg (i.p.) of this nootropic produced an approximately 20% increase in NOS activity in rat brain cortical homogenates but not in hippocampal homogenates; no significant changes were observed in NOS mRNA expression in the cortex and hippocampus. A lower dose of pramiracetam (100 mg/kg i.p.) was ineffective on NOS mRNA expression and enzyme activity. Interestingly, administration of pramiracetam (300 mg/kg i.p.) in rats pretreated (24 h before) with lithium chloride (LiCl) (3 mEq/kg i.p.) yielded a 40% increase in cortical NOS activity. However, in LiCl-pretreated rats this nootropic failed to affect cortical NOS mRNA expression; LiCl (3 mEq/kg i.p.) given alone produced no effect. In conclusion, the present data demonstrate that pramiracetam given alone or in combination with LiCl increases NOS activity in brain cortical homogenates of rats and this may contribute to the mechanisms underlying learning and memory improvement produced by this nootropic.
------------------------------------------------------------------------------------------------------------------------------------------
And an article on NO and the brain:
http://www.sfn.org/i...eAndBrainDamage
Nitric Oxide and Brain Damage.
While researchers actively investigated larger molecules, the diminutive gas, nitric oxide, remained a wallflower. It was thought that the gas had no role in the body or brain. Today, nitric oxide is at center stage. It turns out that the molecule plays a role in a number of beneficial brain and body mechanisms. Recently researchers found evidence that it also can cause damage in the brain. The new understanding of its destructive side may lead to a whole new generation of medical treatments that can battle a variety of brain ailments.
A contributor to smog, nitric oxide (NO) once was known solely for its ability to pollute the environment. It forms in the air when nitrogen burns, for example during the production of car exhaust. Today researchers believe that the gas also can affect the brain.
Starting in the late 1980s, a large number of studies found that NO surprisingly exists in the body and brain and pervasively influences a number of biological functions. While many of its actions are beneficial, sometimes the molecule appears to turn toxic. Scientists are finding evidence that NO participates in the brain cell damage that occurs in a variety of neurological ailments, such as stroke and Parkinson's disease. The new research is leading to:
- Targeted brain cell-protecting therapies that interfere with NO chemistry.
- Clearer insight into the complex behavior of NO.
- A better understanding of how gas compounds can impact biology.
Unfortunately you can get too much of a good thing.
Some researchers believe that many brain disorders can trigger an overproduction of NO. And the excess gas ends the life of brain cells known as neurons.
The first inkling of NO's sinister side came in 1991 when researchers found that they could block the neuron death that normally occurs in a cell model of stroke by inhibiting NO production. Specifically, they blocked the activity of an enzyme, known as nitric oxide synthase (NOS). This enzyme synthesizes the NO gas. Researchers have difficulty blocking NO directly because the gas has a very short lifespan in the neuron.
Additional research on animals also shows that NO is involved in neuron death. For example, studies determined that blocking NOS in the brain impedes the cell death that occurs from stroke as well as in other disorders such as Parkinson's disease.
Researchers now are actively investigating compounds that can derail NOS, in order to create new therapies that will control NO and protect human neurons in a range of brain ailments.
Scientists also are investigating other participants in NO's course of action in order to identify additional treatment targets. One participant that may hold promise is the enzyme called PARP. Some researchers believe that excess NO creates nicks and breaks in the DNA of neurons. The injuries in this important molecule activate PARP, which depletes energy sources in the cell, causing cell death. Scientists found that doses of small molecules that inhibit PARP reduce brain damage in a variety of animal stroke models. In addition, genetically-altered mice that do not produce PARP are protected from the damage of experimentally-induced stroke and Parkinson's disease.
Researchers believe that nitric oxide (NO) forms in neurons following a series of molecular reactions that occur in a matter of milliseconds. Many of the specifics of NO production are still unclear. For example, it's not known how often NO is produced or how involved different participants need to be in order to carry out the production. It's thought that the molecule glutamate can start the process by leaving a neuron and attaching to a molecule lining an adjacent neuron, known as the NMDA receptor. Their union causes calcium molecules to enter the receiving cell. This can trigger the activation of the enzyme NOS, which synthesizes NO. Some researchers believe that NO production normally aids brain function, but overproduction of the gas can kill neurons. A larger, higher resolution version of the graphic is <a href="http://www.sfn.org/s...llus.large.jpg" target="_blank">available here[/url]. (57k)
Illustration by Lydia Kibiuk, Copyright © 1999 Lydia Kibiuk.
Edited by chrono, 25 August 2010 - 04:28 PM.
formatting
