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Dr. Bob is Robert Hsiung, MD,
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Posted by mmcconathy on November 26, 2004, at 22:40:52
In reply to Re: Why arnt there more AD that work on dopamine? » mmcconathy, posted by Larry Hoover on November 26, 2004, at 22:09:45
Wellbutrin works ok with me, althought sometimes lately i've been experiencing intesified thoughts that sometimes are disturbing, like i've lost mental stableness, my thoughts seem out of order. I dont know if this is my own psychological issue, or a side-effect.
Never mind that.But yes i agree that there needs to be a limit, that will not allow euphoria to occur. Just to a normal level.
Any other imputs?
Take Care
Posted by banga on November 27, 2004, at 1:57:43
In reply to Re: Why arnt there more AD that work on dopamine?, posted by linkadge on November 26, 2004, at 22:23:41
Zoloft has a larger effect on dopamine than Wellbutrin?? Is there somewhere I can read up on that? I hadnt heard that before, I wish there were more charts out there about the effects of these drugs out there--they often turn out to be incomplete.
Posted by Larry Hoover on November 27, 2004, at 8:17:53
In reply to Re: Why arnt there more --Linkadge?, posted by banga on November 27, 2004, at 1:57:43
> Zoloft has a larger effect on dopamine than Wellbutrin?? Is there somewhere I can read up on that? I hadnt heard that before, I wish there were more charts out there about the effects of these drugs out there--they often turn out to be incomplete.
According to this database, linkange is quite correct:
http://kidb.cwru.edu/pdsp.phpPut the generic name of the drug in the "test ligand" field.
Sertraline has higher affinity at the D2 receptor and at the dopamine transporter than does bupropion. Lower numbers are higher affinities.
Lar
Posted by linkadge on November 27, 2004, at 9:38:36
In reply to Re: Why arnt there more --Linkadge?, posted by banga on November 27, 2004, at 1:57:43
I will try and locate something, as I have seen charts that try and quantify the degree of neurotransmitter reputake of different drugs.
Actually wellbutrin is thought to work on a strong norepinephrine/weak dopamine reputake system.
I've read a few articles that suggest that at clinical doses, there is more effect of zoloft on dopamine than wellbutrin.
Linkadge
Posted by banga on November 27, 2004, at 11:23:57
In reply to Re: Why arnt there more --Linkadge?, posted by linkadge on November 27, 2004, at 9:38:36
that's really interesting. Zoloft was my first med, 12 years ago, dose was not very high and my depression was not as bad back then, so it has been difficult to compare to my response in more recent years; but sometimes I wonder if it would be--if i decided i need an SSRI around after all--a drig to try again for me.
I have the nice article that compares many SSRIs and tricyclics and the amount of action on each neurotransmitter..they did say Zoloft worked on dopamine, but claimed it was insignificant. But they did not compare to Wellbutrin; and there is certainly room for disagreement on things like this!
Thanks for responses!
Posted by linkadge on November 27, 2004, at 11:40:46
In reply to Re: Why arnt there more --Linkadge?, posted by banga on November 27, 2004, at 11:23:57
I would not say that it is insignificant.
I found the difference between celexa and zoloft was virtually apathy or no apathy.
Linkadge
Posted by KaraS on November 27, 2004, at 17:01:28
In reply to Re: Why arnt there more --Linkadge?, posted by linkadge on November 27, 2004, at 11:40:46
Perhaps there is a synergistic effect with Wellbutrin because of the NE/DA combination whereas Zoloft's serotonergic activity might counterbalance or offset it's dopaminergic activity. Might the end result be more of a dopaminergic effect with Wellbutrin?
I am suggesting this because I believe that I need dopaminergic assistance and I took Zoloft but I was able to discern only a serotonergic effect from it. I felt no motivation, was extremely apathetic and had no sex drive. I realize that others might have a different response to Zoloft but I'm still left wondering about it's net dopaminergic effects.
Posted by linkadge on November 27, 2004, at 17:56:40
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by KaraS on November 27, 2004, at 17:01:28
I understand what you are saying. I have been on celexa for like 5 years (which is extremely selective) and so I notice the slightest changes
Ie, If you were to give me celexa,paxil,proxac,or zoloft I would be able to tell you which one I took.
I will admit that zoloft led to apathy like celexa, but not quite as much.
You are also right about the serotogenic effect surpressing the dopamine effect. This will happen to a certain extent.
And yes there is the effect of norepinephrine/DE corelease with wellbutrin.
I rank the SSRIs in this order for most apathy inducing to least apathy inducing
celexa,
luvox
paxil
zoloft
prozacPaxil and prozac made me irritable (they have effects on NE ??) zoloft made me the most caring. I was unmotivated yes, but I was still able to process emotion of others.
Infact, on zoloft and cofeee I felt really normal.
Linkadge
Posted by linkadge on November 27, 2004, at 17:58:20
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by KaraS on November 27, 2004, at 17:01:28
Oh and one other thing.
Zoloft downregulates beta adrenergic receptors
while celexa does not. This is evidence of some effect on catecholamine.Linkadge
Posted by jujube on November 27, 2004, at 19:33:30
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by KaraS on November 27, 2004, at 17:01:28
See table 3.8 on SSRIs compared to Clomipramine and the "Effect of Uptake of their metabolites in vitro" found at:
http://www.preskorn.com/books/ssri_s3.html#tab3-8Obviously, since Wellbutrin is not a SSRI, it is not on the chart.
If you have already seen this, sorry for the duplication.
Tamara
> Perhaps there is a synergistic effect with Wellbutrin because of the NE/DA combination whereas Zoloft's serotonergic activity might counterbalance or offset it's dopaminergic activity. Might the end result be more of a dopaminergic effect with Wellbutrin?
>
> I am suggesting this because I believe that I need dopaminergic assistance and I took Zoloft but I was able to discern only a serotonergic effect from it. I felt no motivation, was extremely apathetic and had no sex drive. I realize that others might have a different response to Zoloft but I'm still left wondering about it's net dopaminergic effects.
>
>
>
>
Posted by KaraS on November 28, 2004, at 0:04:55
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by linkadge on November 27, 2004, at 17:56:40
> I understand what you are saying. I have been on celexa for like 5 years (which is extremely selective) and so I notice the slightest changes
>
> Ie, If you were to give me celexa,paxil,proxac,or zoloft I would be able to tell you which one I took.
>
> I will admit that zoloft led to apathy like celexa, but not quite as much.
>
> You are also right about the serotogenic effect surpressing the dopamine effect. This will happen to a certain extent.
>
> And yes there is the effect of norepinephrine/DE corelease with wellbutrin.
>
> I rank the SSRIs in this order for most apathy inducing to least apathy inducing
>
> celexa,
> luvox
> paxil
> zoloft
> prozac
>
> Paxil and prozac made me irritable (they have effects on NE ??) zoloft made me the most caring. I was unmotivated yes, but I was still able to process emotion of others.
>
> Infact, on zoloft and cofeee I felt really normal.
>
>
> Linkadge
Linkadge,
From what you said above, Zoloft seemed to be better for you. If that's the case then why are you on Celexa now instead of Zoloft?I personally couldn't tell one SSRI from the others. They all did so little for me. That's too bad since I tolerated them so well (except for Celexa). Maybe someday I may take one of them as part of a cocktail of medications but not on its own.
Kara
Posted by KaraS on November 28, 2004, at 0:06:31
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics » KaraS, posted by jujube on November 27, 2004, at 19:33:30
> See table 3.8 on SSRIs compared to Clomipramine and the "Effect of Uptake of their metabolites in vitro" found at:
>
> http://www.preskorn.com/books/ssri_s3.html#tab3-8
>
> Obviously, since Wellbutrin is not a SSRI, it is not on the chart.
>
> If you have already seen this, sorry for the duplication.
>
> Tamara
>
> > Perhaps there is a synergistic effect with Wellbutrin because of the NE/DA combination whereas Zoloft's serotonergic activity might counterbalance or offset it's dopaminergic activity. Might the end result be more of a dopaminergic effect with Wellbutrin?
> >
> > I am suggesting this because I believe that I need dopaminergic assistance and I took Zoloft but I was able to discern only a serotonergic effect from it. I felt no motivation, was extremely apathetic and had no sex drive. I realize that others might have a different response to Zoloft but I'm still left wondering about it's net dopaminergic effects.
> >
Thanks. I hadn't seen that. Too bad, as you say, that they didn't include other medications in the chart. It would be interesting to compare them.
Posted by linkadge on November 28, 2004, at 0:42:02
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics » jujube, posted by KaraS on November 28, 2004, at 0:06:31
I'm kicking myself in the pants for begging my doctor to swich me back.
It's a mixed bag. On the one hand the prozac, and zoloft were better AD medications for the apathy, but on the other hand they increase certain psychotic features I have.Linkadge
Posted by theo on November 28, 2004, at 8:48:17
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by linkadge on November 28, 2004, at 0:42:02
Prozac can cause a "zombie" like effect on people including myself. I'll find myself staring at the computer screen at nothing and look down at the clock and 15 minutes has gone by. Other SSRI's can indeed cause apathy, but not the trance like state Prozac can cause. Why is this? Is Prozac weaker on NE than Paxil or others?
Posted by ed_uk on November 28, 2004, at 9:19:47
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by theo on November 28, 2004, at 8:48:17
All SSRIs make me apathetic, nothing special about Prozac for me!!
Ed
Posted by linkadge on November 28, 2004, at 10:57:10
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by ed_uk on November 28, 2004, at 9:19:47
That funny cause I found prozac the most the most activating and agitation of the bunch. I could hardly sit still for 5 min.
Linkadge
Posted by theo on November 28, 2004, at 11:18:02
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by linkadge on November 28, 2004, at 10:57:10
Yes, Prozac was activating physically, I increased my time spent in the gym, but mentally I would tend to gaze for long periods of time.
I've read several places Paxil hits NE harder. Paxil made me a little sleepy but I would find myself reading more books and cleaning my house, is this strange or can NE make that much difference?
Posted by ed_uk on November 28, 2004, at 11:30:18
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by theo on November 28, 2004, at 11:18:02
On Paxil I could easily sleep 18 hours a day!
Ed
Posted by linkadge on November 28, 2004, at 11:41:17
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by ed_uk on November 28, 2004, at 11:30:18
Paxil also has a antihistamine effect that can cause sdation but. It does have significant affinity for the norepinephrine reuptake sites.
Paxil actually felt very effexor-like to me (I am sensitive to NE)
Linkadge
Posted by mmcconathy on November 28, 2004, at 13:37:35
In reply to Re: Zoloft vs. Wellbutrin as dopaminergics, posted by linkadge on November 28, 2004, at 11:41:17
From i heard from Larry Hoover, no.
Wellbutrin can make me irrtible, i used to have a problem with motivation, basically laziness, but i was pleasant to just sit and do nothing in harmony. Wellbutrin activates me a bit, but makes me irrtible to where i HAVE to do it, im in worse mood than before.
Adderall does the opposite, i feel positive about doing things.
Even Caffiene is a better treatment than bupropion, sometimes.
I think it works more on NE than DA. Adderall works more on dopamine maybe that's for increased "drive" effects.
Anyways.... i hope they do come with a better dopaminergic soon.
Posted by linkadge on November 28, 2004, at 14:11:22
In reply to Re: Will they come out with more dopaminergics?, posted by mmcconathy on November 28, 2004, at 13:37:35
Not all dopaminergics have abuse potential so I don't see that there will not be some in the near future.
I've never heard of selegeline abuse for instance.
As well certain dopaminer agonists like d1/d2 agonists might proove usefull for motivation without abuse potential.
Linkadge
Posted by pablo1 on November 28, 2004, at 16:44:02
In reply to Re: Why arnt there more --Linkadge? » banga, posted by Larry Hoover on November 27, 2004, at 8:17:53
Can someone explain the results of this. I searched any flavor of dopamine in humans using dopamine% as a wildcard and got almost 2,000 results. I crunched that into excel to sort and there are usually several records for each med, some with very different results. I assume the Ki (nM) column is the important one, indicating the effect the drug has on dopamine. I have no idea what Ki (nM) means, is that agonism or reuptake inhibition. In the recptor column they have either the specific D1, D2, etc or 'Dopamine Transporter' or even some odd ones like 'Dopamine2-like'. Does the transporter comment imply reuptake inhibition?
some familiar meds results:
DOPAMINE D3 Amisulpride 2
DOPAMINE D2 Amisulpride 1
(but I checked not human tests & got huge numbers)
Dopamine Transporter Amphetamine,(+) 25
(not very high?)
Dopamine Transporter d-AMPHETAMINE 21,000
DOPAMINE D1 d-AMPHETAMINE 10,000
DOPAMINE D2 d-AMPHETAMINE 10,000
DOPAMINE D3 d-AMPHETAMINE 10,000
Dopamine Transporter d-AMPHETAMINE 190
Dopamine Transporter d-AMPHETAMINE 116
DOPAMINE D1 Ephedrine,(-) 10,000
DOPAMINE D2 Ephedrine,(-) 10,000
DOPAMINE D5 Ephedrine,(-) 10,000
DOPAMINE D3 Ephedrine,(-) 10,000
Dopamine Transporter Ephedrine,(-) 236
DOPAMINE D5 MDMA 10,000
DOPAMINE D3 MDMA 10,000
DOPAMINE D2 MDMA 10,000
DOPAMINE D1 MDMA 10,000
Dopamine Transporter MDMA 10,000
DOPAMINE D1 MDMA, R(-) 10,000
DOPAMINE D2 MDMA, R(-) 10,000
DOPAMINE D1 METHYLPHENIDATE 10,000
DOPAMINE D2 METHYLPHENIDATE 10,000
Dopamine Transporter METHYLPHENIDATE 50
Dopamine Transporter METHYLPHENIDATE 42
Dopamine Transporter METHYLPHENIDATE 34
Dopamine Transporter METHYLPHENIDATE 21
DOPAMINE D1 METHAMPHETAMINE (+) 10,000
DOPAMINE D2 METHAMPHETAMINE (+) 10,000
Dopamine Transporter METHAMPHETAMINE (+) 25
DOPAMINE D2 BUPROPION 35,000
Dopamine Transporter BUPROPION 1,800
Dopamine Transporter BUPROPION 950
Dopamine Transporter BUPROPION 784
Dopamine Transporter BUPROPION 562
(wide range of results)
DOPAMINE D3 COCAINE 10,000
DOPAMINE D2 COCAINE 10,000
DOPAMINE D5 COCAINE 10,000
DOPAMINE D1 COCAINE 10,000
Dopamine Transporter COCAINE 743
Dopamine Transporter COCAINE 469
Dopamine Transporter COCAINE 331
Dopamine Transporter COCAINE 240
Dopamine Transporter COCAINE 214
DOPAMINE D2 Venlafaxine 35,000
Dopamine Transporter Venlafaxine 10,000
DOPAMINE D2 Venlafaxine 10,000
DOPAMINE D3 Venlafaxine 10,000
DOPAMINE D2 Venlafaxine 10,000
Dopamine Transporter Venlafaxine 7,647So it seems the numbers are all over the place. Can these numbers just be looked at simply or you'd really need to go track down each study to figure out the relevance?
>
> According to this database, linkange is quite correct:
> http://kidb.cwru.edu/pdsp.php
>
> Put the generic name of the drug in the "test ligand" field.
>
> Sertraline has higher affinity at the D2 receptor and at the dopamine transporter than does bupropion. Lower numbers are higher affinities.
>
> Lar
Posted by Larry Hoover on November 28, 2004, at 17:49:56
In reply to Re: neurotransmitter chart » Larry Hoover, posted by pablo1 on November 28, 2004, at 16:44:02
> Can someone explain the results of this. I searched any flavor of dopamine in humans using dopamine% as a wildcard and got almost 2,000 results.
Funny, I got 3212. ;-)
> I crunched that into excel to sort and there are usually several records for each med, some with very different results.
Make sure you're looking at human receptors, whenever possible.
> I assume the Ki (nM) column is the important one, indicating the effect the drug has on dopamine.
Ki is the equiblibrium inhibitor dissociation constant, which has units of nanomolar (nM). You don't need to know more than that nanomolar is very very dilute.
The tendency of any substance to occupy the binding site of a receptor or an enzyme is measured by its tendency to leave the active site, all on its own. The Ki is the concentration of that substance that is required for the receptor to be 50% occupied (at equilibrium, as many binding events are beginning as those that are ending), in the absence of the natural ligand (e.g. dopamine, for the dopamine receptor). The smaller that value for Ki, the higher its affinity must be, as 50% occupancy occurs at lower substrate concentrations.
> I have no idea what Ki (nM) means, is that agonism or reuptake inhibition.
You only know affinity from the Ki. What the drug will do once bound is another matter altogether. A full agonist will give 100% (or even more) of the effect of the natural ligand, if the drug binds there. An antagonist will give zero effect, even when fully bound. (That has the effect of reducing the receptor population, taking some out of commission temporarily.) A partial agonist will give something between 0 and 100% of the normal agonist response. Then there are inverse agonists, which give an opposite response to that expected from binding to that receptor. You can't tell any of this just from the Ki value. All you know is whether or not the drug has a likelihood of sticking onto that receptor.
> In the recptor column they have either the specific D1, D2, etc or 'Dopamine Transporter' or even some odd ones like 'Dopamine2-like'.
I don't know what dopamine-2-like means, (could be a gene variant not yet fully defined), but the transporter is the reuptake pump. So, transporter binding by an antagonist will inhibit reuptake, for example.
> Does the transporter comment imply reuptake inhibition?
Yes. Generally, anything binding to a reuptake pump will slow down its natural activity, as that's all they do.
> some familiar meds results:
> DOPAMINE D3 Amisulpride 2
> DOPAMINE D2 Amisulpride 1The low value indicates very high affinity at those receptor subtypes. If you click on the hotlink reference to the right, you'll be taken to a Pubmed article that shows that the effect is antagonistic. In other words, amisulpride binds very actively at these two receptors, but inhibits them.
> (but I checked not human tests & got huge numbers)
> Dopamine Transporter Amphetamine,(+) 25
> (not very high?)
> Dopamine Transporter d-AMPHETAMINE 21,000
> DOPAMINE D1 d-AMPHETAMINE 10,000
> DOPAMINE D2 d-AMPHETAMINE 10,000
> DOPAMINE D3 d-AMPHETAMINE 10,000
> Dopamine Transporter d-AMPHETAMINE 190
> Dopamine Transporter d-AMPHETAMINE 116These results for amphetamine tell you that the effect is not greatly due to dopamine receptor binding, but is instead due to reuptake inhibition.
Etc.
Lar
Posted by pablo1 on November 28, 2004, at 18:26:45
In reply to Re: neurotransmitter chart » pablo1, posted by Larry Hoover on November 28, 2004, at 17:49:56
OK so the high number means it takes more of the drug to attach to the receptors & the low numbered drugs are stronger. I wonder if this is relative to milligrams or relative to a 'typical recommended dose' which would be more meaningful. Probably it's in relation to milligrams though I'd guess so that's another thing that needs to be calculated to get anything meaningful.
I didn't see many options for norepenephrine, I used a search of 'adrenergenic%' and assume maybe I chose the correct term. Maybe it should have been '%adren%' to capture other possibilities.
Then you'd have to look up the seratonin effects & work a little formula to figure dosage and relative effect of the three (and others...) The chart I've been using is at http://sl.schofield3.home.att.net/medicine/psychiatric_drugs_chart.html and it's very helpful but much simplified. It would be very doable to use the data on the above site and crunch it down into a really usable chart like the one I just mentioned only with real numbers that relate to a typical dose. Maybe add rows if the effects are different at different doses like amisulpride increases dopamine at low doses & blocks it at high doses. When I was going on effexor I wanted to know the effects of dopamine & norep. but the pharmacist was helpless to give any meaningful answers. Of course then each drug effects a different part of the brain more or less so it becomes terribly complicated. No wonder the pdocs just throw something at you & see if it works. Terribly complicated stuff.
>
> The tendency of any substance to occupy the binding site of a receptor or an enzyme is measured by its tendency to leave the active site, all on its own. The Ki is the concentration of that substance that is required for the receptor to be 50% occupied (at equilibrium, as many binding events are beginning as those that are ending), in the absence of the natural ligand (e.g. dopamine, for the dopamine receptor). The smaller that value for Ki, the higher its affinity must be, as 50% occupancy occurs at lower substrate concentrations.
Posted by Larry Hoover on November 28, 2004, at 20:55:14
In reply to Re: neurotransmitter chart, posted by pablo1 on November 28, 2004, at 18:26:45
> OK so the high number means it takes more of the drug to attach to the receptors & the low numbered drugs are stronger. I wonder if this is relative to milligrams or relative to a 'typical recommended dose' which would be more meaningful. Probably it's in relation to milligrams though I'd guess so that's another thing that needs to be calculated to get anything meaningful.
It's probably more related to blood concentration, which you can get from the pharmacokinetics of the individual drug monographs.
> I didn't see many options for norepenephrine, I used a search of 'adrenergenic%' and assume maybe I chose the correct term. Maybe it should have been '%adren%' to capture other possibilities.
There's only one reference for norepinephrine, the norepinephrine transporter. If you pull down the menu on the right hand side of query page, you can see all the different receptors for which there are data.
> Then you'd have to look up the seratonin effects & work a little formula to figure dosage and relative effect of the three (and others...) The chart I've been using is at http://sl.schofield3.home.att.net/medicine/psychiatric_drugs_chart.html and it's very helpful but much simplified. It would be very doable to use the data on the above site and crunch it down into a really usable chart like the one I just mentioned only with real numbers that relate to a typical dose.This database is not really for the average person's interest. It's strictly comparisons of receptor affinities, not drug effectiveness.
> Maybe add rows if the effects are different at different doses like amisulpride increases dopamine at low doses & blocks it at high doses. When I was going on effexor I wanted to know the effects of dopamine & norep. but the pharmacist was helpless to give any meaningful answers. Of course then each drug effects a different part of the brain more or less so it becomes terribly complicated. No wonder the pdocs just throw something at you & see if it works. Terribly complicated stuff.
Understatement.
Lar
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