• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

Toluene... an antidepressant, and what's more...

^Now that is interesting. Risperidone primarily acts on the 5-HT2A & D2 receptors and there is the 'NMDA hypothesis' concerning schizoform disorders. In the old days, it was believed that it was too much dopamine in certain areas of the brain that were the issue but now they believe that it's the NMDA pathways that are influencing this balance. I know several new drugs that work on the NMDA receptors have shown clinical promise.

I do remember reading that in cerebrospinal fluid of sufferers, there was always either more dopamine metabolites or too little aspartic acid. Interesting, no?
 
It doesn't surprise me really, the effects of ether were almost indistinguishable from N2O for me, it seems like a lot of volatile gasses are NMDAr-antagonists.

Now get me some Trichloroethane, I'm bored as fack!
 
In that it's expensive or in that it's really good? My money is on the former alone. Nitrous, with it's effects on the opioid system is probably about as good as it gets.
 
Should i suspect lesions considering the regular olfactory hallucinations?

I've worried enough about it, but i don't do anything about it :\

I really would like to see a neurologist about it.. to see if these manifestations are seizure auras, lesions or nothing at all

Just looking for some encouragement i guess...
 
Nitrous, with it's effects on the opioid system
Click to expand...

Do you have any references handy? This is the first of this that I've yet heard.

ebola
 
Hammilton said:
In that it's expensive or in that it's really good? My money is on the former alone. Nitrous, with it's effects on the opioid system is probably about as good as it gets.
Click to expand...

No, I just mean it's a sparkling dry white wine from a particular region in France (although Xexon-ware wine-cups have been discovered also).

Yes - just the price.

It appears to be somewhat more potent than N2O with a MAC of 72% (N2O is 120). I suppose if that kind of thing is your 'cup of tea' so to speak, then methoxyflurane is the Everclear of the class (MAC 0.2). It's used for emergency analgesia in Australia. I think there are only 2 companies worldwide who supply it & one of them is some anonymous industrial unit in Victoria.


OK - back to the antidepressant activity of NMDA antagonists. I know K has been researched in this field, but is there much known about the reason for it's effectiveness? Sounds odd. I believe it, but nonetheless it's slightly strange to me.
 
fencamfamine said:
OK - back to the antidepressant activity of NMDA antagonists. I know K has been researched in this field, but is there much known about the reason for it's effectiveness? Sounds odd. I believe it, but nonetheless it's slightly strange to me.
Click to expand...

Yup. Paper in Science about it recently.
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists.
Nanxin Li, et. al. Science 329, 959 (2010)

Basically, mTOR induced growth of new dendritic spines, particularly in the PFC. This new spine growth seemed to be responsible. Also interesting to note that only low doses were effective at this.

I have the paper if you don't have access.
 
Modulatory effects of the NMDAr's, like synaptic plasticity in the form of LTP in the hypocampus has been seen to "normalize" the NMDAr's from over excitation of glutamate in response to stress and depressive illnesses.
 
My guess is that it works in the same way electroshock therapy does, it zaps some brain cells which makes you too out of it to care about your depression.
 
I thought the idea was to zap off braincells, and hopefully zap off the ones that are making the patient insane or depressed.
 
ECT Mechanism of Action

The aim of ECT is to induce a therapeutic clonic seizure (a seizure where the person loses consciousness and has convulsions) lasting for at least 15 seconds. Although a large amount of research has been carried out, the exact mechanism of action of ECT remains elusive. The main reasons for this are that the human brain can not be studied directly before and after ECT and therefore scientists rely on animal models of depression and ECT, with major limitations. While animal models are acknowledged to model merely aspects of depressive illness, human and animal brains are very similar at a molecular level, enabling detailed study of the molecular mechanisms involved in ECT[1]

There is a vast literature on the effects of Electroconvulsive Shock (ECS) in animals. In animal models of depression, particularly "Learned helplessness" and "Social defeat", there is evidence of pruning of normally dense synaptic connections in the hippocampus, a richly connected area deep in the temporal lobe which is vital in controlling both mood and memory.[98] ECS has been shown to increase levels of Brain-derived neurotrophic factor (BDNF) and Vascular Endothelial Growth Factor (VEGF) in the rodent hippocampus.[99] This reverses the toxic effects of depression on this area of the brain, increasing both new synapse formation and the formation of new brain cells (hippocampal neurogenesis). Both these effects have been noted to be present in antidepressant-treated animals, however they are neither necessary nor sufficient for antidepressant response. ECT is a more robust inducer of these neuroplastic effects than antidepressants.[100] Electroconvulsive Therapy (ECT) has also been shown to increase serum brain-derived neurotrophic factor (BDNF) in drug resistant depressed patients.[101] This suggests a common molecular mechanism of action, albeit in need of much further study.
Click to expand...

We literally don't know what ECT does to the brain precisely.
 
Also, on the topic of xenon, would the increased potency essentially mean that it would "hit you harder" than an equal amount of nitrous oxide? I remember when rangrz posted that trip report of one of the flurane anaesthetics, I believe it was enflurane. He inhaled a few drops out of a bag and it totally clobbered him. Interesting report.
 
I was only joking when I mentioned xenon & methoxyflurane. If your not in an operating suite with all of the attendant safety factors, it's simply dangerous. Metthoxyflurane, in particular, has resulted in quite a few deaths from people trying to 'catch a buzz'. At least N2O isn't so potent that you black out & drown in 3 inches of water (or whatever becomes of you). It's VERY potent (MAC 0.2!) and a few drops is quite enough. Induction is quite slow so people do too much.

Please just don't.
 
ebola? said:
Do you have any references handy? This is the first of this that I've yet heard.

ebola
Click to expand...

There are so many of them, just click here. Google has a ton of results.

Br. J. Anaesth. (1995) 74 (6): 670-673. doi: 10.1093/bja/74.6.670
> compares xenon to nitrous, though naloxone had no effect in this study. Xenon significantly increases the time for response to auditory stimuli, which is interesting, and nitrous didn't! Perhaps this means it makes nitrous' whanging effect or whatever they call it much stronger? Interesting nonetheless!

Anesth Prog 38:206-211 1991
> Looks at nitrous' effect on beta endorphin and met-enkephalin in the brain stem and pituitary, both of which are increased following administration of the gas.

Lichtigfeld FJ, Gillman MA (1996). "Role of dopamine mesolimbic system in opioid action of psychotropic analgesic nitrous oxide in alcohol and drug withdrawal". Clinical Neuropharmacology 19 (3): 246–51. doi:10.1097/00002826-199619030-00006.

Psychotropic analgesic nitrous oxide (PAN) has been used successfully in the treatment of alcohol and drug withdrawal in > 15,000 cases. It is an opioid and thus the first gaseous member of the opioid family. We propose the existence of two mutually antagonistic opioid systems as underlying addictive withdrawal states; mu and kappa. PAN as a multipotent opioid activates these systems. Dopamine (DA) activity in the nucleus accumbens appears to be controlled by kappa- and mu-receptors, with mu enhancing and kappa inhibiting release. In morphine and alcohol withdrawal, there is severe inhibition of dopamine release from nucleus accumbens. We thus infer that a probable major therapeutic effect of PAN is in modulating this dopamine system, thereby correcting the severe deficit in dopamine release found in withdrawal states. This has been achieved without any transfer of addiction to PAN in any of the treated patients because of modulation of DA in the nucleus accumbens by PAN. This effect may also explain its anticraving action.

> They maybe go a bit far calling it an opioid, but it certainly seems to have an effect on opioid receptors.
 
Hammilton said:
Anesth Prog 38:206-211 1991
> Looks at nitrous' effect on beta endorphin and met-enkephalin in the brain stem and pituitary, both of which are increased following administration of the gas.
Click to expand...

could this possibly hold some similarity to the claims that methoxetamine has an effect on the opiod system? it certainly feels like the memory of what opiodergic activity feels like.... but?:\
 
fencamfamine said:
I was only joking when I mentioned xenon & methoxyflurane. If your not in an operating suite with all of the attendant safety factors, it's simply dangerous. Metthoxyflurane, in particular, has resulted in quite a few deaths from people trying to 'catch a buzz'. At least N2O isn't so potent that you black out & drown in 3 inches of water (or whatever becomes of you). It's VERY potent (MAC 0.2!) and a few drops is quite enough. Induction is quite slow so people do too much.

Please just don't.
Click to expand...

I figured the regular crowd in ADD would be smart enough to understand the dangers of such chemicals, but thank you anyway for the disclaimer. Never can be too careful in a world chock full of idiots.
 
hammilton said:
There are so many of them, just click here. Google has a ton of results.
Click to expand...

Thanks. I prefer you vastly to search engines. :)

ebola
 
Personally, I think this thread is inappropriate. I agree that its quite an interesting observation that Toluene may have antidepressant qualities, but this thread could clearly be misinterpreted and lies counter to the spirit of harm reduction.
 
You must log in or register to reply here.
Top