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

  • N&PD Moderators: Skorpio | someguyontheinternet

Various dopaminergic drugs

polymath

polymath

Bluelight Crew
Joined
Nov 4, 2010
Messages
1,890
Location
Northern Europe
There are several kinds of drugs that have dopaminergic effects... There are DA releasers/reuptake inhibitors(amphetamine, cocaine), direct DA agonists(bromocriptine, apomorphine), substances that increase DA production in cells(L-dopa) and then there are MAO-B inhibitors that inhibit the breakdown of DA.

The effects of these are not similar at all. For example, large doses of bromocriptine, apomorphine and L-dopa cause nausea because of activation of DA receptors in the chemoreceptor trigger zone in fourth ventricle. Cocaine, amphetamine or selegiline don't have this effect even in large doses, even though you would expect that these drugs would increase synaptic DA in the CTZ, too.

Also, direct agonists and L-dopa only rarely cause euphoria similar to amphetamines or cocaine... It seems like the effect of dopaminergic stimulants is more specific to the mesolimbic area of the brain, while the direct agonists and L-dopa cause dopaminergic effects indiscriminately in all areas of the brain.

The only similarity between the drugs seems to be that both amphetamine and L-dopa cause paranoid psychosis if given in large doses.

What causes these differences between different dopaminergics? Or is this something that no one currently knows the answer to?

With cholinergic drugs, for example, the situation is a lot simpler. The effects of ACh overactivity are the same, whether they be caused by a mixture of nicotine/muscarine agonists or by a cholinesterase inhibitor.
 
It seems like the effect of dopaminergic stimulants is more specific to the mesolimbic area of the brain, while the direct agonists and L-dopa cause dopaminergic effects indiscriminately in all areas of the brain.
Click to expand...

So in the case of amphetamines doesn't dopamine release happen in all areas of the brain ?

Also, classic psychedelics are considered to be Dopamine agonists apart from serotonin agonists , no ?
 
Long story short: these drugs may preferentially bind to receptors in certain areas of the brain, require metabolism to become active (which happens mainly in the substantia nigra in the case of L-DOPA IIRC), bind to different receptors/proteins aside from dopamine receptors, and of course DA release/reuptake inhibition/breakdown will all result in slightly different concentrations in certain areas of the brain.

L-DOPA and amphetamine do share several similarities in regards to psychosis, but there is also quite a few differences in them as well particularly involving the concentrations of NE involved. Then you have to look at amphetamine's "secondary" pharmacological features such as TAAR binding and weak 5HT release compared to L-DOPA which also has some secondary features itself.

In pharmacology we have a tendency to oversimplify things to basic categories like DRA/SSRI/ or MAOI when in fact the compounds in question have generally more complex mechanisms of action. Sort of like comparing cocaine to Ritalin, both are DRI's but by no means exclusively DRI's.
 
^ That was mostly what I was thinking... I wonder what would the effects be like if L-dopa or bromocriptine was microinfused directly to someones mesolimbic dopamine pathway.

There have actually been some reports about people abusing L-dopa for euphoria, but those have been isolated occurrences and most people don't find the effects euphoric.
 
^ It could be caused by some impurity in the coke getting in the bloodstream... Does smoking crack have the same side effect on those people?
 
norepinephrine is very important in reward and drugs of abuse, its why apomorphine and miraprex and dopamine agonists dont cause alot of euphoria but amphetamine does.
 
polymath said:
^ It could be caused by some impurity in the coke getting in the bloodstream... Does smoking crack have the same side effect on those people?
Click to expand...

I have seen people indulge in quite spectacular feats of emesis after smoking crackPersonally I have felt nausea after a few stimulants (amphetamine, fencamfaminr and mdpv), the sort of nausea that comes after doses of opiates. No other feelings of not being too well, except from the nausea, which also like opiates is immediately relieved by vomiting. The fact that opiates cause nausea via dopaminergic action in the ctz and it's similar to stimulant induced nausea (well in me and a few oeople I've asked) makes me think that there's some activity in the ctz due to these agents.


One other thing, I read somewhere that in people taking parkinson's medications, the thing that made them feel worse were things that would usually cause disgust. Again, only personal experiences, but after taking a dose of one of the above stims, try doing something like washing out a dustbin or changing a cat litter. I did and the thought of how revolting the dustbin would be had me gagging (needless to say wash was postponed). This has happened several times whereas if no stims are involved, the job gets done without having to retire early (not the nicest of jobs, but one that doesn't induse nausea in me)

As I said, it seems too much of a coincidence for me
 
^ I agree, MDPV actually made me hurl a few times and after recent trials of Camfetamine(Fencamfamine's little brother I believe),I commented to a friend : "It's a lovely drug....apart from the pervasive nausea."
 
^ Does your route of admin lead to a very rapid rise in plasma levels? I've found that if you're feeling a bit ropey (eg a bit hungover) it's best to go for a route that doesn't ramp up the plasma concn too quickly, to avoid the nausea
 
Not really, hearing all the horror stories about the nasal burn from CFA has made me a bit careful and so far I've only gone for oral ROA.I certainly wouldn't want to risk IV'ing it untill I've seen a lot more about it. The nausea seems to be fairly consistent throughout the period I can feel activity. It's a shame, coz it's otherwise really rather a nice stimulant. Maybe gastro-intestinal distress is just an intrinsic effect of this compound.
 
fastandbulbous said:
I have seen people indulge in quite spectacular feats of emesis after smoking crackPersonally I have felt nausea after a few stimulants (amphetamine, fencamfaminr and mdpv), the sort of nausea that comes after doses of opiates. No other feelings of not being too well, except from the nausea, which also like opiates is immediately relieved by vomiting. The fact that opiates cause nausea via dopaminergic action in the ctz and it's similar to stimulant induced nausea (well in me and a few oeople I've asked) makes me think that there's some activity in the ctz due to these agents.


One other thing, I read somewhere that in people taking parkinson's medications, the thing that made them feel worse were things that would usually cause disgust. Again, only personal experiences, but after taking a dose of one of the above stims, try doing something like washing out a dustbin or changing a cat litter. I did and the thought of how revolting the dustbin would be had me gagging (needless to say wash was postponed). This has happened several times whereas if no stims are involved, the job gets done without having to retire early (not the nicest of jobs, but one that doesn't induse nausea in me)

As I said, it seems too much of a coincidence for me
Click to expand...

There's a "vomit center/ chemoreceptor trigger zone" of the CNS that's very sensitive to DA, probably depends on the individual and drugs in question regarding nausea. This link connects to some interesting reading for those who wish to learn about the subject.

Part of me thinks it might be a obscure part of the "fight or flight response", but I haven't looked to deep into it.
http://en.wikipedia.org/wiki/Domperidone
 
FandB said:
The fact that opiates cause nausea via dopaminergic action in the ctz and it's similar to stimulant induced nausea (well in me and a few oeople I've asked) makes me think that there's some activity in the ctz due to these agents.
Click to expand...

Do you have links to any research demonstrating that the mechanism of opioid induced nausea is dopaminergic? I have a good many friends who are stimulant enthusiasts, who handle high doses well, exhibiting marked euphoria and compulsive behaivor while lacking nausea, but who experience severe nausea from opioids accompanied by little euphoria.

ebola
 
MasterOfDeception said:
So in the case of amphetamines doesn't dopamine release happen in all areas of the brain ?

Also, classic psychedelics are considered to be Dopamine agonists apart from serotonin agonists , no ?
Click to expand...


Most are pretty selective for serotonin. AFAIK LSD and a few others have some affinity for DA receptors but not as strong as for 5HT-2a, generally not enough to be considered significant at most recreational doses.
 
ebola? said:
Do you have links to any research demonstrating that the mechanism of opioid induced nausea is dopaminergic? I have a good many friends who are stimulant enthusiasts, who handle high doses well, exhibiting marked euphoria and compulsive behaivor while lacking nausea, but who experience severe nausea from opioids accompanied by little euphoria.

ebola
Click to expand...

Only in terms of their activity on the dopaminergic system, nothing specific about actual vomiting. That said, they do seem to have an awful lot in common, such as once you've puked you feel worlds better (unlike say food poisoning where you can puke 10 times and still not feel better). As well as that, the opiates are structurally very close to emetine and apomorphine, both of which work on the ctz to induce vomiting via dopamine.

As I said, it seems a bit more than a co-incidence
 
You must log in or register to reply here.
Top