5HTP vs L-Tryptophan

[VelocideX]

From this thread

http://www.ncbi.nlm.nih.gov:80/entr...eve&db=pubmed&dopt=Abstract&list_uids=9232674
here is a paper which implies that 5-HT1 activation is a key component of dxm's antitussive (anticoughing) effect.

DXM appears to inhibit the uptake and metabolism of 5-HT in platelets:
http://www.ncbi.nlm.nih.gov:80/entr...ieve&db=pubmed&dopt=Abstract&list_uids=238000

Treatment with reserpine, a non-neurotoxic 5-HT depleter, inhibits the antitussive effect of DXM:
http://www.ncbi.nlm.nih.gov:80/entr...eve&db=pubmed&dopt=Abstract&list_uids=2965557

l-Tryptophan administration appears to increase the antitussive effects of DXM:
http://www.ncbi.nlm.nih.gov:80/entr...eve&db=pubmed&dopt=Abstract&list_uids=2384857

DXM appears to release 5-HT in the brainstem:
http://www.ncbi.nlm.nih.gov:80/entr...eve&db=pubmed&dopt=Abstract&list_uids=1636059

 

[Adam X]

That's extremely interesting, I've never heard anything like that before (re dopamine-serotonin ratio). You're implying that tolerance isn't just due to some period of neurotransmitter excess but stems from an imbalance in the neurotransmitter ratio, which in theory could be altered by the appropriate drug from the opposite class?

The brain constantly tries to maintain homeostasis. Serotonin-dopamine are fairly intimately linked, if the ratio of one to the other is disrupted the brain makes adaptive changes. Usually this change results in a dulling of the sites of action of amphetamine, instead of a boosting of the serotonin (which could create problems itself). Trick the brain into thinking that serotonin and dopamine levels are in proper proportion and you slow the process of tolerance. Look at MDMA tolerance/addiction compared to d-amp or d-meth... Which would you rather have to deal with?

Do you think this applies equally well to the noradrenic and cholinergic systems?

I don't know. I would guess no, since tolerance to the physiological stimulant effects of amp decreases more rapidly than tolerance to the behavioral.

Do you have any references which might support this notion?

Not at the moment, this is just a theory of mine. I might dig around though, but I don't see how I'd be able to find anything really conclusive either way. Plus I have a chem midterm coming up, maybe when that's done I'll have more time to poke around.


X

 

[VelocideX]

Nice theory in any repect

 

[junglelove]

That is a very viable pathway: usually serotonin acts as a negative feedback, check upon dopamine. excitation of 5-ht2a receptors by mdma is a trigger to dopamine release, while 5-ht2a antagonists preclude or delay DA release. Notably mdma also binds to 5-ht1a which inhibits serotonin firing and decreases tryptophan hydroxylase. given that mdma has a much higher binding affinity to 5-ht sites than DA it seems to be the case that via desensitization and inhibited production of 5-ht (inhibit tr hydroxylase) less DA is stimulated to be released because less 5-ht receptors are available for agonism. modulating 5-ht receptor sites might be an alternative pathway to combat tolerance buildup - that might be a reason why DXm works so well along with ssri's (via 5-ht inhibition and receptor upregulation)

 

[BilZ0r]

hang on, hang on, hang on.
Adam, correct me if I'm wrong you're saying, DXM could/does inhibit METH tolerance, by acting as an SSRI. Now you must be saying that by acting as an SSRI, its increasing 5-HT levels? See I just wonder. METH is going to be releasing some 5-HT anyways, not to much granted, but the SSRI action of DXM might cancel out the releasing abbility, and kinda equal things out.

MDMAs affinity for 5-HT1A has gotta be pretty tiny, but I don't get the rest of your explanation.