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direct dopamine agonist?

ebola?

Bluelight Crew
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Is there any chemical agent out there which is a direct agonist at dopamine receptors (particularly in the mesolimbic reward pathway) without causing a release of dopamine, inhibition of reuptake, an increase in synthesis, or activity at other catecholamine receptors?

Would such a chemical be fun? What role does activity at norepinephrine sites play in the pleasurable aspects of psychomotor stimulants?
(if this topic is insufficiently advanced, feel free to move this to other drugs or something).

ebola
 
I'm curious about this as well.

But I would also like to know if a chemical causing release of dopamine and/or inhibition of reuptake and/or an increase in synthesis (or any other activity at catecholamine receptors). Would a chemical with such attributes have the ptential to be pleasure? Obviously, bupropion is an inhibitor of dopamine reuptake but I believe this causes only a marginal increase in the availability of dopamine (not possible, so don't take that as fact).

One more thing...does anyone know a some sort of online medical dictionary. I am very interested in this forum and believe I could learn a great deal. I would also love to be an active participant, but some topics go over my head. This type of dictionary could help me understand more by clarifying some of the terminology for me. Although, Dictionary.com has been semi-sufficient so far. Thanks.
 
>> I would also like to know if a chemical causing release of dopamine and/or inhibition of reuptake and/or an increase in synthesis (or any other activity at catecholamine receptors). >>

Well, most people think d-amphetamine is pretty fun. :)
Of course, this also has a similar effect at nor-epi' sites.
...
The primary reason I'm really asking about a clean direct-agonist at dompamine sites is to tease-apart the effects of dompine agonism (direct or indirect) and nor-epi' agonism, since since dopamine is later metabolized into nor-epi' and taken up at nor-epi' sites.

ebola
 
GBR analogues possibly. It is difficult to guage whether or not they are fun, def. not recreational.
 
hmmm...what is GBR, and how could they be fun but not recreational?

ebola
 
Oh it is some SDRI (the S is for selective and not serotonin). Two model compounds are in the latter stages of clinical trials. It is likely that these compounds will be marketed as the methadone of cocaine addiction by healthcare professionals. Sort of misleading since the duration of action is not especiably loooooooooong. There was a dummy to work around this issue though. Basically by havin' a hydroxy group on the phenylpropyl chain then esterifying the compound (cf soap) and polymerizing, drug reported to last 1 whole month. Use google.
 
Directly acting agonists

All of the ones mentioned so far are not directly acting agonists, but ones causing dopamine release, or re-uptake inhibitors (GBR is the designation for research compounds evaluated by a particular pharmaceutical company; it's usually followed by a number designation).

As that's the case (and because I'm lazy), I've scanned in a couple of pages from the Tocris catalogue detailing which compounds are agonists at various dopamine receptors, and a table detailing where they're mainly found. To identify any compound, put the name (eg SKF 38393) into search engines and it'll pull up any refs for it, and you can follow on from there


You'll have to download it to read it as I had to get the size under 100k



Rather than use a new reply for an off-topic q: It's not really a song, it's just the good Captain playing with words between the tracks on Trout Mask Replica
 
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Thanks FB...that is what I was looking for.
OT: did you get your name from a captain beefheart song?

ebola
 
If you go to tocris, you can view the dopamine receptor ligands they have...

As far as I'm awear, most non-selective dopaminergic agonists just cause vomiting... at least initially. I don't remember any reporting apomorphine is that fun.
 
Rules

^^ Didn't want to put a link to the Tocris site, in case it was viewed as naming a source, even though they wont even respond to you unless you contact them through a university or similar type of research establishment.

BilZ0r, I remember a while ago you mentioned something about William Burroughs and his views on pharmacology. I've got "The William Burroughs Reader", and in one chapter, he list the sucess he's had in treating opiate WD with various drugs, and he stated that apomorphine was one of the best(?!!). OK if you don't mind projectile vomiting a la Linda Blair in the Exorcist!
 
Dihydrexidine looks like it might be ok if you like Dinosaur dope.
 
hmmm...quinpirole appears to be the selective D2 agonist of choice in the literature...

still trying to figure out what you mean by dinosaur dope. :)...I would like to get high with a stegasaurus.

ebola
 
has to do with coupling to signalling pathways

hey,
this isn't really a complete theory, but i'd say it would serve as a crude explanation here.

take your dopamine receptor. when dopamine (DA) binds, a conformational (shape) change is induced in the cytoplasmic domain of the receptor which causes appropriate G-proteins to be attracted to the dopamine receptor (DAR) to get activated. For example, the G-protein "Gs" activates an enzyme (adenylate cyclase) which in turn produces the second messenger signalling molecule cAMP.
There are around 4 or 5 G proteins which are commonly used (and likely many more,) which all exert different effects. It is possible and likely that receptors may activate more than one G protein, and also miscelaneous "g-protein associated proteins," which will alter the activity of G-proteins.

The conformational change induced by the agonist on the receptor is a function of the structure of the agonist. What I am saying, is that a DA agonist, such as quinpirole, likely induces a different DAR conformation than DA will. This in turn will lead to the recruitment of a different set of signalling molecules to the receptor.
This means that a different response in the post synaptic cell may be elicted by various agonists.

More evidence of this kind of thing can be evidenced by differential tolerance mechanisms to different opiod agonists. Morphine does not cause receptor downregulation, where etorphine does. (It is proposed the morphine tolerance may be mediated by regulating levels of adenylate cyclase. this is similar to cannabinoid tolerance, actually.)
These differential tolerance mechanisms can be interpreted as the result of recruitment of signalling proteins by various mu opioid receptor - ligand complexes.

if anyone has any comments on that i'd love to hear them
 
excellent.
very informative.
looks like this forum is attracting...well, the opposite of riff-raff.

ebola
 
"Agonist directed trafficking", interesting stuff, although the mack daddy of directable receptors is my fav, the 5-HT2A... with good potency through G(alpha-q), G(alpha-12/13), and G(alpha-11)... to PLC, PLA2 and PLD respectively...
 
hey Dope_User, i have the same problem (understanding alot of the terminology of all new topics). I use this medical dictionary -i found it when using dictionary.com, when you type in medical terms or things relating to pharmacology, it usually links to up to it. I find it very helpful in understanding terms (about all things related to medicine, not just pharmacology).

http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=&action=Search+OMD

:)
 
ebola! said:
Is there any chemical agent out there which is a direct agonist at dopamine receptors (particularly in the mesolimbic reward pathway) without causing a release of dopamine, inhibition of reuptake, an increase in synthesis, or activity at other catecholamine receptors?

ebola

Dopamine is a pretty good dopamine receptor agonist.

I think it's likely that any drug that is an agonist of the dopamine receptor will increase the reuptake of dopamine through negative feedback (in an attempt to re-establish equilibrium). :D
 
they use dopamine in hospitals to raise blood pressure and its uncontrolled. But from what i've heard, its lacking in any pleasure or high whatsoever.
 
I read somewhere that Parkinsons patients had been abusing L-dopa, ie taking large dosages of the stuff (12g). It is totally true that increased dopamine is the internal cue that governs drug addiction.
 
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