N&PD Moderators: Skorpio
Metaphit
Nagelfar
Bluelight Crew
Is it the tree I'm barking up or the issue I'm chasing? 
P, I hate how the lowercase makes a "razz" emoticon, I use it for "tongue-in-cheek") Because a 'presynaptic mechanisms' the inverse of a NMDA receptor affect *is* what I am looking for in that instance.
specialspack
Bluelighter
Is it the tree I'm barking up or the issue I'm chasing?
P, I hate how the lowercase makes a "razz" emoticon, I use it for "tongue-in-cheek") Because a 'presynaptic mechanisms' the inverse of a NMDA receptor affect *is* what I am looking for in that instance.
Sorry, what is it you're looking for? You've lost me.
Nagelfar
Bluelight Crew
In terms of the other thread it is whatever way anesthetic gasses differ in NMDA type affinity, without their indiscriminate affinity for sigma and other types, that is it. If metaphit does the inverse of this from "presynaptic mechanisms", that is the right direction.
specialspack
Bluelighter
My point is that the wiki post you are using as your sole basis for the way anesthetic gases differ from the NMDA antagonism is flawed. They don't work by simple channel block.
If metaphit works by pre-synaptic mechanisms, which is just speculated, then it has nothing to do with the NMDA receptor at all! So I don't see the connection with anesthetic gases. Obviously this is difficult to square with the early acylation in vitro paper though.
Nagelfar
Bluelight Crew
Speculation is always the most fruitful starting place.
Anesthetic gasses may have nothing to do with receptors directly either, but the possibility of downstream NMDA type functionality in common is a good place to start looking.
specialspack
Bluelighter
Speculation is only worthwhile if you have some pointers. Wild speculation is useless. What reason at all do we have to think that there is any functionality in common between metaphit and anaesthetic gases..? 8)
Nagelfar
Bluelight Crew
Check out the orvinol class of opioids. They add any number of branched tertiary alcohol substituent to the 7 position of their C ring for highly potent efficacy (near the 6 position where a branch renders mu-3 subtype affinity, as an example). This might be thought of as essentially isolating alcohol's indiscriminate but extremely low (otherwise) affinity for opioid analgesic effect. Using its pervasive style of docking in a much more narrow and deliberate way.
Were solvents similarly bound as a branch to a molecule which excluded their indiscriminate binding to other sites but in turn specified it's binding into its one active specificity over its others as a free structure, potentially I can see similarity. Rendering it to work as an adjunct to 'binding' or, in the case I have in mind, *near binding* inherent in the rest of the molecule itself (i.e. needing to be PCP-like) for the site in question.
It needn't bind to the PCP receptor to do this, PCP likely has all manner of downstream NMDA affinity due to its near conformations. Much as isomers of other NMDA antagonists work on other neurotransmitter systems, or how the different monoamines have cross over affinity and effects.
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specialspack
Bluelighter
I understand the idea you have of binding the anesthetic gas to another molecule to therefore position it for better interaction with the NMDA receptor. But if metaphit doesn't interact with the NMDA receptor and instead via some presynaptic mechanism I see no similarity there...
PS good work on updating the wiki! You should include the original ref about the irreversible bonding to the PCP site - http://www.ncbi.nlm.nih.gov/pubmed/2982662
Nagelfar
Bluelight Crew
I was using "downstream NMDA affinity" to insinuate "some presynaptic mechanism" in my own loose way.
Done.