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Caramboxin

Nagelfar

Nagelfar

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After reading about how similar anatoxin-a is to other agonist drugs (it is a nicotinic acetylcholine receptor agonist, a precursor can be cocaine, and there are several examples of phenyltropanes that are nicotinic agonists too) I wondered what other compounds that are neurotoxins might be close to relating to a pharmacore of drugs of abuse and be parent compound to them. I ran into caramboxin; an NMDA receptor agonist (not antagonist) that has a phenylalanine skeleton, and made me think of whether glutamate antagonists or such as thpse might have DA releasing properties of some variety (I know many NMDAR antagonists overlay DRIs and have some residual properties of that, but I've yet to see one viable as a DRA)

Caramboxin.svg


Any observations of possible changes that may bridge that gap?
 
I would guess this does not have stimulant effects. if phenylalanine is inactive, then I don't why this would be active. I don't even think it would make it into the brain, unless it happens to be transported by an amino acid transporter.
 
serotonin2A said:
I would guess this does not have stimulant effects. if phenylalanine is inactive, then I don't why this would be active. I don't even think it would make it into the brain, unless it happens to be transported by an amino acid transporter.
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Well apparently it does, since it is a fatal neurotoxin. Just reminded me of the 2C class of psychedelics, I found it interesting that it was a NMDAR "agonist" of all things (excitotoxicity)
 
That sort of polyhydroxylated, highly polar compound reminds me of some of the other NMDA agonists. They're all amino acids.

I don't think they are workable drugs though. Good tool compounds, maybe.
 
What would the mental effects be of (a very low dose of) NMDA agonists?
 
immad said:
What would the mental effects be of (a very low dose of) NMDA agonists?
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I'm totally assuming here but with respect to how other drugs are likened when the come down, withdrawal, etc., of heavy use hits. I'd assume like how heavy ketamine, or PCP or 'robotripper' addicts feel who come off of it after near dependency and very consistent use for prolonged periods of time; perhaps not as harsh (unless you live in that perpetual K-hole, which some, I know not how, good gracious do I ever not know, but some indeed, do).

Probably like a, metaphorical & rhetorical not in any way literal: shot of narcan to a opioid naive person unless under the influence of DXM or such, then like a shot of narcan to a opioid dependent person; just equivalent to the ketamine "hang-over" and not to the "opioid" subjective feeling one way or the other. I hope this isn't too much confusion; by which I mean feeling *nothing* like narcan etc., but I mean about PAWS onset, etc. with regard to the NMDAR & glutamate system. I know glutamate wires the reward pathway, perhaps additionally it makes one take in and store as pertinent the unnecessary environment at the time of dosing and thus be a "stressor" in that capacity.

Of course, this is just my wild guess, if anyone with better first or second hand or has known a study of such knowledge, please feel free to make my comment from the peanut gallery a moot point. I'd welcome being educated myself so as to not just blow hot air on the issue in the future.
 
A low enough dose of an NMDA agonist might actually have strong antidepressant, 'after glowing' properties (provided there occurs some sensitization / up regulation of NMDAR), and the ketamine associated antidepressive effect has been linked to a subunit of NMDARs afaik. But with just a bit too much (depending on the individual), oversensitivity to stimuli, feelings of stress and anxiety, lowered threshold for impulsivity and emotional outbursts / anger. Maybe even seizures. At least my speculation.

But then again it's possible than NMDA receptors don't upregulate that much or quick at all (a question I've posted in another thread) and the positive/negative after effects are due to independent and/or downstream mechanisms... one possibility being the dopaminergic activity of ketamine and PCP as well as the (reasonably strong) serotonergic activity of MXE / DXM with the latter also being noradrenergic and sigmaergic (also moderately opioidergic in high doses).

And part of it might be entirely psychological. But since the pathways used by dissociatives are involved in neuronal plasticity, could there be some overlapping...? Coming off K or MXE is usually nothing uncomfortable for me, with prolonged MXE (and much stronger, DXM) use there is a bit of SSRI withdrawal. Memantine feels different and more disturbing (not for everyone either), but since it's a comparatively weak antagonist I now suspect other mechanisms to be responsible.

Regarding the DA thing, I thought that by (partially) inhibiting / blocking the NMDARs, dopaminergic neurotransmission would get facilitated anyway even w/o direct DRI/DRA properties... or am I wrong? And DA rebound / withdrawal is nothing to enjoy..
 
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