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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by jay2112 on January 26, 2022, at 13:06:08
Just to clarify, stims et al act primarily on the D4 receptor. D4 receptors also are low density in Parkinson's. I personally react very well to stims et al, as do most people. D1-2 agonism agitates me.
https://pubmed.ncbi.nlm.nih.gov/24484981/
(read the entire article, if you can)
Jay
Posted by linkadge on January 26, 2022, at 17:15:22
In reply to Stims, Cocaine, Nicotine target D4, posted by jay2112 on January 26, 2022, at 13:06:08
Thanks for posting. Just to push back a bit though, that abstract doesn't seem to suggest that stimulants have preferential affinity for d4 (vs other dopamine receptors). That being said, I've heard that d4 receptors may in fact be the target for ADHD, and (according to this abstract) addiction.
Linkadge
Posted by rjlockhart37 on January 26, 2022, at 19:40:31
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by linkadge on January 26, 2022, at 17:15:22
isnt D1 receptors connected to parkinson's disease?
i know if someone doennt have enough dopamine, it results in movement disorders, similar to the shuffle with haliparidol
Posted by rjlockhart37 on January 26, 2022, at 19:42:08
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by rjlockhart37 on January 26, 2022, at 19:40:31
correction: 'haloperidol'
low dopamine results in movement disorders. I know this is not what the article on D4 receptors are abuot but i think parkinson's is associated with D1 receptors. \
Link would know anything about this?
Posted by undopaminergic on January 27, 2022, at 8:37:59
In reply to Stims, Cocaine, Nicotine target D4, posted by jay2112 on January 26, 2022, at 13:06:08
> Just to clarify, stims et al act primarily on the D4 receptor. D4 receptors also are low density in Parkinson's. I personally react very well to stims et al, as do most people. D1-2 agonism agitates me.
>
> https://pubmed.ncbi.nlm.nih.gov/24484981/
>
> (read the entire article, if you can)
>
> JayI intend to read the article at some time.
As Linkadge pointed out, the abstract does not suggest psychostimulants act primarily on dopamine D4 receptors. Rather, the article is a review of the role of DA D4-receptors in psychostimulant addiction.
Stimulants are indirect dopamine agonists that do not target any particular receptor directly, but they increase synaptic dopamine, which in turn acts on the full range of DA receptors. If there is a receptor they act "primarily" on, it would be D2 simply because that is the most common DA receptor.
-undopaminergic
Posted by rjlockhart37 on January 27, 2022, at 15:12:57
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by rjlockhart37 on January 26, 2022, at 19:40:31
ok no more off the subject questions, just curious also parkinson's they don't get a reward from dopamine because there's hardly any
Posted by jay2112 on January 27, 2022, at 22:08:13
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by undopaminergic on January 27, 2022, at 8:37:59
> > Just to clarify, stims et al act primarily on the D4 receptor. D4 receptors also are low density in Parkinson's. I personally react very well to stims et al, as do most people. D1-2 agonism agitates me.
> >
> > https://pubmed.ncbi.nlm.nih.gov/24484981/
> >
> > (read the entire article, if you can)
> >
> > Jay
>
> I intend to read the article at some time.
>
> As Linkadge pointed out, the abstract does not suggest psychostimulants act primarily on dopamine D4 receptors. Rather, the article is a review of the role of DA D4-receptors in psychostimulant addiction.
>
> Stimulants are indirect dopamine agonists that do not target any particular receptor directly, but they increase synaptic dopamine, which in turn acts on the full range of DA receptors. If there is a receptor they act "primarily" on, it would be D2 simply because that is the most common DA receptor.
>
> -undopaminergic
>Well, it's in the wording, but they do (stims) act on D4 in a manner other dopamine agonists don't. My point being, targeting D4 receptors is therapeutic, and if a chemical which only targets D4 were available, it may avoid side effects of the other targets.
Posted by undopaminergic on January 28, 2022, at 8:09:50
In reply to Re: Stims, Cocaine, Nicotine target D4 » undopaminergic, posted by jay2112 on January 27, 2022, at 22:08:13
> >
> > Stimulants are indirect dopamine agonists that do not target any particular receptor directly, but they increase synaptic dopamine, which in turn acts on the full range of DA receptors. If there is a receptor they act "primarily" on, it would be D2 simply because that is the most common DA receptor.
> >
> > -undopaminergic
> >
>
> Well, it's in the wording, but they do (stims) act on D4 in a manner other dopamine agonists don't.
>What do you mean by "other dopamine agonists"? For example, according to Wikipedia, pramipexole, a direct dopamine agonist, has some affinity for D4.
> My point being, targeting D4 receptors is therapeutic, and if a chemical which only targets D4 were available, it may avoid side effects of the other targets.
>It would avoid effects mediated by other dopamine receptors, but that would include all effects and not just adverse effects.
-undopaminergic
Posted by jay2112 on January 28, 2022, at 19:50:34
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by undopaminergic on January 28, 2022, at 8:09:50
> > >
> > > Stimulants are indirect dopamine agonists that do not target any particular receptor directly, but they increase synaptic dopamine, which in turn acts on the full range of DA receptors. If there is a receptor they act "primarily" on, it would be D2 simply because that is the most common DA receptor.
> > >
> > > -undopaminergic
> > >
> >
> > Well, it's in the wording, but they do (stims) act on D4 in a manner other dopamine agonists don't.
> >
>
> What do you mean by "other dopamine agonists"? For example, according to Wikipedia, pramipexole, a direct dopamine agonist, has some affinity for D4.
>
> > My point being, targeting D4 receptors is therapeutic, and if a chemical which only targets D4 were available, it may avoid side effects of the other targets.
> >
>
> It would avoid effects mediated by other dopamine receptors, but that would include all effects and not just adverse effects.
>
> -undopaminergic
>IF you read the entire article, there are selective D4 agonists (i.e. NOT pramipexole) that are EXCLUSIVE to the D4 receptor. They have separate and differentiated effects. What part of that don't you understand?
Posted by jay2112 on January 28, 2022, at 20:07:11
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by jay2112 on January 28, 2022, at 19:50:34
And stims, cocaine, nicotine agonize the D4 receptor much more than most available dopamine agonists...which was the point of the article. There is something exclusive about the D4 receptor that may lead to better treatment for addiction and adhd.
Jay
Posted by undopaminergic on January 29, 2022, at 8:05:14
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by jay2112 on January 28, 2022, at 19:50:34
> > > >
> > > > Stimulants are indirect dopamine agonists that do not target any particular receptor directly, but they increase synaptic dopamine, which in turn acts on the full range of DA receptors. If there is a receptor they act "primarily" on, it would be D2 simply because that is the most common DA receptor.
> > > >
> > > > -undopaminergic
> > > >
> > >
> > > Well, it's in the wording, but they do (stims) act on D4 in a manner other dopamine agonists don't.
> > >
> >
> > What do you mean by "other dopamine agonists"? For example, according to Wikipedia, pramipexole, a direct dopamine agonist, has some affinity for D4.
> >
> > > My point being, targeting D4 receptors is therapeutic, and if a chemical which only targets D4 were available, it may avoid side effects of the other targets.
> > >
> >
> > It would avoid effects mediated by other dopamine receptors, but that would include all effects and not just adverse effects.
> >
> > -undopaminergic
> >
>
> IF you read the entire article, there are selective D4 agonists (i.e. NOT pramipexole) that are EXCLUSIVE to the D4 receptor. They have separate and differentiated effects. What part of that don't you understand?
>I said I *intend* to read it -- I haven't yet. No need to be rude.
> And stims, cocaine, nicotine agonize the D4 receptor much more than most available dopamine agonists...which was the point of the article.
>If that is indeed a (major) point of the article, I think they would mention it in the abstract.
> There is something exclusive about the D4 receptor that may lead to better treatment for addiction and adhd.
>Yes, the article proposes that D4 antagonism may be of use in treating stimulant addiction. That would seem to imply that *agonism* is particularly relevant to the *induction* of addiction.
-undopaminergic
Posted by jay2112 on January 29, 2022, at 11:59:28
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by undopaminergic on January 29, 2022, at 8:05:14
Sorry if I was a little edgy...my anxiety has been horrible. But, you get the picture of what I was trying to say.
Jay
Posted by Lamdage22 on January 29, 2022, at 13:19:50
In reply to Re: Stims, Cocaine, Nicotine target D4 » undopaminergic, posted by jay2112 on January 29, 2022, at 11:59:28
Would you think that targeting the D4 is more acceptable if prone to psychotic symptoms than D2? I must say, mood wise I really need dopamine, but thoght wise, not at all.
Posted by jay2112 on February 10, 2022, at 22:39:40
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by Lamdage22 on January 29, 2022, at 13:19:50
> Would you think that targeting the D4 is more acceptable if prone to psychotic symptoms than D2? I must say, mood wise I really need dopamine, but thoght wise, not at all.
I honestly can't answer absolutely, so ymmv, but I have read on some schizophrenia support websites, that some schizophrenics take very small amounts of some stimulants (in particular, amphetamine/vyvanse..it apparently binds less tighter than ritalin to dopamine receptors) to offset a bit of the effects of antipsychotics.
But, caution, of course.
Jay
Posted by Lamdage22 on March 8, 2022, at 6:10:01
In reply to Re: Stims, Cocaine, Nicotine target D4 » Lamdage22, posted by jay2112 on February 10, 2022, at 22:39:40
Yeah I have made such bad experiences with stimulating compounds that I won't touch any of that. I may not have euthymic mood and motivation, but at least I am sane now.
Posted by Lamdage22 on March 8, 2022, at 6:12:36
In reply to Re: Stims, Cocaine, Nicotine target D4, posted by Lamdage22 on March 8, 2022, at 6:10:01
Ok I realize depression and anxiety is not exactly sanity, but it is more so than psychosis.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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