<p>I have quite a bit of experience understanding the gluatmate system and in particular the NMDA receptor subtypes. NMDA receptors are a highly complex system, which effect neuro function in multipule and often opposite ways. NMDA receptors modulate virtually the location,composition and activity of almost all receptor types this is because they have heavily implicated in Long term potentiation and Long Term depression, which are terms to describe the strengthing and weakening of the interactions between neurons,The wikipedia articles have a good basic cover of this concept.</p>
<p>Nmda receptors are composed of multipule subunits that each have there own pore, THe main three are NR1A,NR2A NR2B. NR1a. NR1a is rather simple it is similar to an cAMP recetpor in that it only allows monovalent cations to enter, this means that this receptor is not involved with a change in LTP or LTD although it fasiclitates LTP and LTD via the other subunits, in other words it passes a signal, and in adults it plays an important role in keeping neural circiuts connected</p>
<p>The NR2(x)s play a different role, and that role depends whether or not there expressed on a synapse. For this discussion I shall limit talk to those NMDA receptors that are expressed on the syanpse.
The NR2A activity mediates quick actting and long term depression of the connection between neurons, From how I understand it thought is the turning off of particular connections on usually a short term basis. So the product of a thought and how it is expressed, is expressed by what in the system is still running after the said thought(this is grossly simplified). Therefore blocking the NR2a reduces the ability to hold a thought, and unfortunately the body doesnt upregulate NR2a activity in response to antagonists. Other systems do move them back and slowly they will reform. This is the heart of the Neurodamage of DMX and PCP.</p>
<p>[NMDA</a> and AMPA Receptors](<a href=“http://www.sumanasinc.com/webcontent/animations/content/receptors.html]NMDA”>NMDA and AMPA Receptors)</p>
<p>Incidentally, I’ve doing research on NMDA receptors and their function</p>
<p>So what do you think would happen if we blocked the NMDA receptors?
Do you think this would be a serious problem? </p>
<p>And what would happen if you combined an NMDA antagonist and an Alpha-2 adrenergic receptor agonist?</p>
<p>More to the point, I’ve been looking into agmatine supplementation (agmatine sulfate), and found an abstract i shall share:</p>
<p>Recent evidence suggests that agmatine, which is an intermediate in polyamine biosynthesis, might be an important neurotransmitter in mammals. Agmatine is synthesized in the brain, stored in synaptic vesicles in regionally selective neurons, accumulated by uptake, released by depolarization, and inactivated by agmatinase. Agmatine binds to alpha2-adrenoceptors and imidazoline binding sites, and blocks NMDA receptor channels and other ligand-gated cationic channels. Furthermore, agmatine inhibits nitric oxide synthase, and induces the release of some peptide hormones. As a result of its ability to inhibit both hyperalgesia and tolerance to, and withdrawal from, morphine, and its neuroprotective activity, agmatine has potential as a treatment of chronic pain, addictive states and brain injury.</p>
<p>And also, ‘Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine’ - here is the abstract:</p>
<p>Receptor imidazoline 2 (I(2)) is one of the imidazoline receptors with high affinity for [(3)H]-idazoxan. Receptor I(2), being classified into I(2A) and I(2B) subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I(2), displaying high similarity of sequence with monoamine oxidase-B (MAO-B), is structurally related to MAO-B, but the I(2) imidazoline binding site (I(2)BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I(2). Accumulating evidence have revealed that the activation of receptors I(2) may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamate-induced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate (NMDA) receptor, inhibiting all isoforms of nitric oxide synthase (NOS), and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.</p>
<p>Thoughts?</p>
<p>no one smart here??</p>
<p>We’re just intelligent enough to know that not everyone is interested in every topic in the universe : )</p>
<p>Take a look at [Extrasynaptic</a> NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways - Nature Neuroscience](<a href=“http://www.nature.com/neuro/journal/v5/n5/abs/nn835.html]Extrasynaptic”>Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways | Nature Neuroscience) You should be able to get the full text within the campus network. Basically it is saying that while synaptic Nr2b are very good for memory the extrasynaptic counterparts regulate the strongest aging pathway in the human body.</p>
<p>Blocking specific types of NMDA receptors may be beneficial to certain types of neurological diagnoses. Autism/aspergers is a disease of excess long term potentiation in the basal glanlia and hippocamus. This can be sourced from the valopric acid model. You are going to need to familiarize yourself with long term potentiation and long term depression. Long term potentiation is caused by fairly extreme glutamate based excitoxicity in the first 6 months of life. Autism is highly associated with minimicrocolumns and about double the NMDA receptors of neurotypicals, which are the requirements for extreme intelligence but unfortunately they are conferring their own liabilities to insult.</p>