![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 5 to 29 of 70. Go back in thread:
Posted by daizy on March 3, 2003, at 10:10:41
In reply to Dopamine agonists, posted by Michael Bell on March 1, 2003, at 18:57:36
> I'm trying to get an idea of the effectiveness of dopamine-related medication in people with Social Anxiety. If you have SA and have taken these types of meds, please name the drug and what the effects were. Thanks!
I think someone said that effexor was a dopamine agonist, however it mad my anxiety much worse. Does this mean that my anxiety is not caused by an increase in dopamine? I thought that effexor was also supposed to increase serotonin and norepinephrine? Im getting confused here, sorry! If effexor made my anxiety worse, what meds do I need to calm me down? Dopamine, noradrenaline, and seratonin antagonists? are they benzo's? Also when I am calm, I am more depressed. HELP!
I dont understand myself!!!!!!!!!! ha ha ha !!
Posted by djmmm on March 3, 2003, at 17:32:14
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 3, 2003, at 10:10:41
To clear something up...There is a difference between agonists/antagonists and reuptake blockers.
effexor is not a dopamine agonist...in fact, the only dopamine agonists available, are used for Parkinsons...some include Bromocriptine, pergolide, pramipexole, ropinirole, piribedil, Levodopa, Amantadine, Lisuride.
MAOIs can act as indirect agonists, because the increase in tyramine acts as a norepinephrine agonist (increase in blood pressure)
Effexor has little effect on dopamine...it is primarily an serotonin and norepinephrine reuptake blocker.
any drug that effects GABA will likely calm you down.
http://salmon.psy.plym.ac.uk/year2/psy221anxiety/psy221anxiety.htm
Posted by KrissyP on March 3, 2003, at 17:52:52
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 3, 2003, at 10:10:41
Hi, Effexor-XR has been approved for GAD-I'm not sure about SA. I'm sure it falls into the category though? Effexor has worked for my social anxiety and my general anxiety=2 of the same? From what I know, Effexor works on all 3-dopamine, serotonin, and norepinephrine. I had no luck on SSRI's which work only on Serotonin. I don't know if I am of any help to you here,but how long have you been on the Effexor that you are still full of anxiety???? Please get back to me. It's been a long day-but I want to help.
To be continued........
Kristen:-)
-------------------------------------------------I'm trying to get an idea of the effectiveness of dopamine-related medication in people with Social Anxiety. If you have SA and have taken these types of meds, please name the drug and what the effects were. Thanks!
I think someone said that effexor was a dopamine agonist, however it mad my anxiety much worse. Does this mean that my anxiety is not caused by an increase in dopamine? I thought that effexor was also supposed to increase serotonin and norepinephrine? Im getting confused here, sorry! If effexor made my anxiety worse, what meds do I need to calm me down? Dopamine, noradrenaline, and seratonin antagonists? are they benzo's? Also when I am calm, I am more depressed. HELP!
>
> I dont understand myself!!!!!!!!!! ha ha ha !!
Posted by medlib on March 3, 2003, at 18:15:32
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 3, 2003, at 10:10:41
Hi Daizy--
Effexor is a weird drug--not an SSRI, but sort of a sequential TCA. At low dose levels E. affects serotonin reuptake. At mid-level doses it affects primarily norepinephrine-transmitting neurons, though it still retains significant serotonin action. At high doses (300mg/day and up) it has a weak effect on dopamine. Some docs feel that E.'s effect on dopamine is too small to be of clinical significance.
From your reaction to E., I would guess that you're taking a mid-level dose (somewhere in the 150-275 range?) where the NE effect predominates. I haven't read the applications for E. as an anti-anxiety agent, but I would think that the recommended dose range would have to be quite low (where only serotonin is affected) or quite high (where, supposedly, dopamine effects kick in).
Anxiety is not one of my multiple problems; but, if it were, and I was offered a choice between, say, Effexor and Klonopin for it, I wouldn't have to think for more than a few seconds before choosing Klonopin. Others on this board have posted some helpful links on SA; you might want to google the archives for them. Do let your pdoc know about your reaction to E.
Hope you find something that works!---medlib, who's ridden musical meds merry-go-round too long.
Posted by Michael Bell on March 3, 2003, at 19:26:29
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 3, 2003, at 10:10:41
> > I'm trying to get an idea of the effectiveness of dopamine-related medication in people with Social Anxiety. If you have SA and have taken these types of meds, please name the drug and what the effects were. Thanks!
>
> I think someone said that effexor was a dopamine agonist, however it mad my anxiety much worse. Does this mean that my anxiety is not caused by an increase in dopamine? I thought that effexor was also supposed to increase serotonin and norepinephrine? Im getting confused here, sorry! If effexor made my anxiety worse, what meds do I need to calm me down? Dopamine, noradrenaline, and seratonin antagonists? are they benzo's? Also when I am calm, I am more depressed. HELP!
>
> I dont understand myself!!!!!!!!!! ha ha ha !!
Daizy, an agonist potentiates increases dopamine/effects of dopamine, whereas antagonist would inhibit dopamine. In my situation, and in most situations I've read about (this board included), drugs that primarily increase dopamine (or effectiveness of dopamine) make anxiety symptoms worse in people with SP. The reason I'm trying to get an idea of the effectiveneness of these types of drugs on SP is because I'm convinced dopamine levels/transmission has a role in SP, but I can't put my finger on it. By the way, If you're looking to for calmness, try a drug that works on GABA, if your doc is cool with it.Also, I have a theory on neurochemical cause of Social Phobia, but it's quite long. Let me know if you want to hear it, and I'll post it. Thanks.
Posted by KrissyP on March 3, 2003, at 19:58:14
In reply to Re: Dopamine agonists, posted by djmmm on March 3, 2003, at 17:32:14
Effexor does have an effect on Dopamine-enough-some is better than none here. Effexor ALSO affects GABA no?
Get back to me please,
Kristen:-)
-------------------------------------------------To clear something up...There is a difference between agonists/antagonists and reuptake blockers.
effexor is not a dopamine agonist...in fact, the only dopamine agonists available, are used for Parkinsons...some include Bromocriptine, pergolide, pramipexole, ropinirole, piribedil, Levodopa, Amantadine, Lisuride.
MAOIs can act as indirect agonists, because the increase in tyramine acts as a norepinephrine agonist (increase in blood pressure)
Effexor has little effect on dopamine...it is primarily an serotonin and norepinephrine reuptake blocker.
any drug that effects GABA will likely calm you down.
http://salmon.psy.plym.ac.uk/year2/psy221anxiety/psy221anxiety.htm
Posted by KrissyP on March 3, 2003, at 20:02:30
In reply to Re: Dopamine agonists » daizy, posted by medlib on March 3, 2003, at 18:15:32
okay. I don't get what you are saying here. please explain. In one sentence you say>"At high doses (300mg/day and up) it has a weak effect on dopamine", and in the next sentence you say this,"or quite high (where, supposedly, dopamine effects kick in)." a weak effect at high doses, but quite high where dopamine effects kick in? I do not get this. I am seriously interested in this as I take Effexor-XR and am wondering what this talk of Dopamine is all about. Please?
Anyone? LOL
Kristen:-)> Hi Daizy--
>
> Effexor is a weird drug--not an SSRI, but sort of a sequential TCA. At low dose levels E. affects serotonin reuptake. At mid-level doses it affects primarily norepinephrine-transmitting neurons, though it still retains significant serotonin action. At high doses (300mg/day and up) it has a weak effect on dopamine. Some docs feel that E.'s effect on dopamine is too small to be of clinical significance.
>
> From your reaction to E., I would guess that you're taking a mid-level dose (somewhere in the 150-275 range?) where the NE effect predominates. I haven't read the applications for E. as an anti-anxiety agent, but I would think that the recommended dose range would have to be quite low (where only serotonin is affected) or quite high (where, supposedly, dopamine effects kick in).
>
> Anxiety is not one of my multiple problems; but, if it were, and I was offered a choice between, say, Effexor and Klonopin for it, I wouldn't have to think for more than a few seconds before choosing Klonopin. Others on this board have posted some helpful links on SA; you might want to google the archives for them. Do let your pdoc know about your reaction to E.
>
> Hope you find something that works!---medlib, who's ridden musical meds merry-go-round too long.
Posted by Maximus on March 3, 2003, at 21:30:34
In reply to Re: Dopamine agonists » djmmm, posted by KrissyP on March 3, 2003, at 19:58:14
> Effexor does have an effect on Dopamine-enough-some is better than none here. Effexor ALSO affects GABA no?
> Get back to me please,
> Kristen:-)
Hi Kristen,Djmmm has already answered perfectly to your questions and so the others. Anyway, here it goes...
Effexor is an SNRI. The is the first Serotonin and Norepinephrine reuptake inhibitor. Its action on DA (at 375 mg and more) is quite insignificant. The mechanism of action of Effexor is unrelated to GABA. Effexor XR has been approved for the treatment of Depression and Generalized Anxiety Disorder (GAD).
Good luck!
Max.
Posted by KrissyP on March 3, 2003, at 21:40:38
In reply to Re: Dopamine agonists » KrissyP, posted by Maximus on March 3, 2003, at 21:30:34
Hi Max, I got ya- you know there are so many posts that I read yours before Djmmm had already answered perfectly to my questions. Thank you for being so smart and helpful:-)
Kristen------------------------------------------Hi Kristen,
Djmmm has already answered perfectly to your questions and so the others. Anyway, here it goes...
Effexor is an SNRI. The is the first Serotonin and Norepinephrine reuptake inhibitor. Its action on DA (at 375 mg and more) is quite insignificant. The mechanism of action of Effexor is unrelated to GABA. Effexor XR has been approved for the treatment of Depression and Generalized Anxiety Disorder (GAD).Good luck!
Max.
Posted by not exactly on March 4, 2003, at 2:42:07
In reply to Dopamine agonists, posted by Michael Bell on March 1, 2003, at 18:57:36
> I'm trying to get an idea of the effectiveness of dopamine-related medication in people with Social Anxiety. If you have SA and have taken these types of meds, please name the drug and what the effects were. Thanks!
Well, there's been lots of interesting and informative posts in this thread, but so far NOBODY that actually has SA AND has really benefitted from a true dopamine-boosting med has posted their experience. So I'll try to fill that void.
I have SA plus atypical depression. While I've found some things that have helped with just the SA - benzo's, Neurontin, even alcohol - the ONLY meds that have EVER helped with BOTH my SA and depression were dopamine meds. And unless my depression is helped, socializing is still unpleasant even if it isn't anxiety-provoking. Mirapex (a dopamine agonist), Ritalin (a dopamine reuptake inhibitor), Selegiline patch (MAO inhibitor that increases dopamine), and Dexedrine (a dopamine releaser) all worked wonders for me. I became a happy extrovert instead of a bummed-out recluse. In contrast, anything which acted on serotonin (such as an SSRI) was a disaster. Norepinephrine meds (such as the TCA Desipramine) weren't much better, until I added Buspar (which boosts - you guessed it - dopamine!).
I can't say whether these dopamine meds would help someone who had SA WITHOUT atypical depression. In fact, I'm reluctant to claim my experience is generalizable to ANYONE else. My reaction to meds - which ones work and which ones don't - seems to be pretty unique. But anyway, you now have one datapoint, FWIW.
- Bob
Posted by daizy on March 4, 2003, at 7:44:45
In reply to Re: Dopamine agonists, posted by Michael Bell on March 3, 2003, at 19:26:29
> Daizy, an agonist potentiates increases dopamine/effects of dopamine, whereas antagonist would inhibit dopamine. In my situation, and in most situations I've read about (this board included), drugs that primarily increase dopamine (or effectiveness of dopamine) make anxiety symptoms worse in people with SP. The reason I'm trying to get an idea of the effectiveneness of these types of drugs on SP is because I'm convinced dopamine levels/transmission has a role in SP, but I can't put my finger on it. By the way, If you're looking to for calmness, try a drug that works on GABA, if your doc is cool with it.
>
> Also, I have a theory on neurochemical cause of Social Phobia, but it's quite long. Let me know if you want to hear it, and I'll post it. Thanks.
Thanx for trying to explain everyone! However I think im more confused that I was before!(if thats possible!)I have to say I have more of a panic disorder, and depression, but anxiety first! Because of previous drug use, I got my depression, if you know Michael, how do drugs Like E work on the brain? Well SNRI and SSRI didnt work for me, am now on TCA and has worked better, Im still hoping to find a med that will work better though! Which drugs work on GABA?
Do you know any links that might explain these things to me? I hate to keep asking, sorry!
I would like to hear your theory??????????
Thanx ;-)
Posted by KrissyP on March 4, 2003, at 11:23:26
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 4, 2003, at 2:42:07
Please? what does FWIW mean LOL:-)
Anyone know?
Kristen
> > I'm trying to get an idea of the effectiveness of dopamine-related medication in people with Social Anxiety. If you have SA and have taken these types of meds, please name the drug and what the effects were. Thanks!
>
> Well, there's been lots of interesting and informative posts in this thread, but so far NOBODY that actually has SA AND has really benefitted from a true dopamine-boosting med has posted their experience. So I'll try to fill that void.
>
> I have SA plus atypical depression. While I've found some things that have helped with just the SA - benzo's, Neurontin, even alcohol - the ONLY meds that have EVER helped with BOTH my SA and depression were dopamine meds. And unless my depression is helped, socializing is still unpleasant even if it isn't anxiety-provoking. Mirapex (a dopamine agonist), Ritalin (a dopamine reuptake inhibitor), Selegiline patch (MAO inhibitor that increases dopamine), and Dexedrine (a dopamine releaser) all worked wonders for me. I became a happy extrovert instead of a bummed-out recluse. In contrast, anything which acted on serotonin (such as an SSRI) was a disaster. Norepinephrine meds (such as the TCA Desipramine) weren't much better, until I added Buspar (which boosts - you guessed it - dopamine!).
>
> I can't say whether these dopamine meds would help someone who had SA WITHOUT atypical depression. In fact, I'm reluctant to claim my experience is generalizable to ANYONE else. My reaction to meds - which ones work and which ones don't - seems to be pretty unique. But anyway, you now have one datapoint, FWIW.
>
> - Bob
>
>
>
Posted by KrissyP on March 4, 2003, at 11:34:17
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 4, 2003, at 7:44:45
Hi, Yeah! Can someone tell me what meds work on GABA? I was told by a doc-I needed one of them and it would work on me. Some GABA reason. Anyone know?
Thanks,
Kristen:-)
> > Daizy, an agonist potentiates increases dopamine/effects of dopamine, whereas antagonist would inhibit dopamine. In my situation, and in most situations I've read about (this board included), drugs that primarily increase dopamine (or effectiveness of dopamine) make anxiety symptoms worse in people with SP. The reason I'm trying to get an idea of the effectiveneness of these types of drugs on SP is because I'm convinced dopamine levels/transmission has a role in SP, but I can't put my finger on it. By the way, If you're looking to for calmness, try a drug that works on GABA, if your doc is cool with it.
> >
> > Also, I have a theory on neurochemical cause of Social Phobia, but it's quite long. Let me know if you want to hear it, and I'll post it. Thanks.
>
>
> Thanx for trying to explain everyone! However I think im more confused that I was before!(if thats possible!)
>
> I have to say I have more of a panic disorder, and depression, but anxiety first! Because of previous drug use, I got my depression, if you know Michael, how do drugs Like E work on the brain? Well SNRI and SSRI didnt work for me, am now on TCA and has worked better, Im still hoping to find a med that will work better though! Which drugs work on GABA?
>
> Do you know any links that might explain these things to me? I hate to keep asking, sorry!
>
> I would like to hear your theory??????????
>
> Thanx ;-)
>
Posted by not exactly on March 4, 2003, at 16:24:14
In reply to Re: Dopamine agonists » not exactly, posted by KrissyP on March 4, 2003, at 11:23:26
Kristen,
> Please? what does FWIW mean LOL:-)
FWIW = "for what it's worth"
BTW, FYI see:
http://www.dr-bob.org/babble/20010122/msgs/52652.html
very handy, IMHOHTH,
Bob
Posted by noa on March 4, 2003, at 19:39:11
In reply to Re: Dopamine agonists » KrissyP, posted by not exactly on March 4, 2003, at 16:24:14
I don't see HTH on the list--what is it?
Posted by KrissyP on March 4, 2003, at 19:50:41
In reply to Re: Dopamine agonists » not exactly, posted by noa on March 4, 2003, at 19:39:11
Ya got me-I'm gonna go look:-)just finished a few posts.......
Kristen
> I don't see HTH on the list--what is it?
Posted by Franz on March 4, 2003, at 21:43:04
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 4, 2003, at 7:44:45
Hi,
I am getting interested in this issue of dopamine and social phobia.
I found there is an European drug (sold OTC in US) called citicholine that increases acetylcholine and dopamine. Wether it increases dopamine in the right place i do not know.
See:
http://lansbury.bwh.harvard.edu/da_reviews_2002.htmciticholine, when administered, undergoes a quick transformation to cytidine and choline, which are believed to enter brain cells separately and provide neuroprotection by enhancing PtdCho synthesis; similar effect may be expected to occur in glaucomatous RGC. Furthermore, citicholine stimulates some brain neurotransmitter systems, including the dopaminergic system
A a side note, with due respect, to prevent Dr Bob aborting this post, I do not understand why importing a product that is sold OTC as a nutritional supplement or whatever in US can be illegal to import (I am referring to the picamilon thread, picamilon is available in the US as a supplement, as well as citicholine also known as CDP-choline).
Posted by Michael Bell on March 4, 2003, at 23:01:38
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 4, 2003, at 7:44:45
Daizy, this is what I think about Social Phobia and neurotransmitters. This theory comes from my own experience, discussions in chat rooms and surfing the net for countless hours. I'll take the transmitter systems one at a time.
Serotonin: High levels: linked with harm avoidance and anxiety, including General Anxiety Disorder. Low levels: linked with some forms of depression, obsessions, deviant thoughts and aggression. I don't believe serotonin is a major player in SP, though it's probably involved on some level (maybe levels are slightly high), uin a complex way we don't know about. My main reason for this belief comes from my own experience as well as what I've encountered regarding SSRIs. One common result that I have found across many chatboards and various studies is that SSRIs do NOT help with SP, and in fact often make the symptoms worse. Those that have noticed an effect often say that they feel emotionally numb as a result of taking these medications. My own feeling is that a medication that removes anxiety through dulling of emotions may be "effective" to some degree, but not in a pleasant way. An interesting things about serotonin - it increases when we "freeze" in frightful situations (similar to mind going blank in social settings)
Norepinephrine -- since this is the fight or flight neurotransmitter, it probably also has a role in SP. Caffeine induces panic attacks in people with SP twice as much as people without SP. Also, beta blockers inhibit norepinephrine from reaching receptors, and are useful for people with performance anxiety. However, studies have shown that people with generalized SP actually have similar NE levels to "normal" people. Also, beta blockers are not very effective for generalized SP. Our receptors are probably hypersensitive to NE, so that we have stronger reactions to situations that should only cause minimal stress.
GABA: I believe most of the evidence points to GABA dysfunction as being the primary culprit in SP. Here's why: The two most effective prescription drugs for SP are Klonopin and Nardil. No other drugs come close. KLONOPIN - works by enabling GABA to bind more easily to its receptors. Klonopin sometimes works so well that it causes disinhibition in some patients, the very opposite of SP. NARDIL - one of the older, irreversible MAOIs, it increases the levels of dopamine, serotonin and norepinephrine in the body and brain. However, other MAOIs, such as Parnate, do the same, and are not nearly as effective as Nardil for SP. The difference is Nardil also a powerful inhibitor of the enzyme that breaks down GABA. I believe it is this action on GABA that makes Nardil such an effective tool. The two other substances that I have heard miraculous results about are ALCOHOL and GHB. In my own experience, alcohol is the single most effective substance I have ever tried for SP, too bad it's dangerous! Most researchers attribute the "wellbeing" effect of alcohol to be due to its potentiation of GABA, however there is also some increased dopamine transmission that takes place as well. The effects of GHB are two-fold. First, it increases the effectiveness of GABA for several hours, causing feelings of wellbeing and disinhibition. Over the course of these hours, it also blocks the transmission of dopamine, causing dopamine levels to build up in the brain. Then the user falls asleep and all the built up dopamine is released, causing the user to wake up refreshed and alert. So here we have four drugs, all which act primarily on GABA, and they are the most effective drugs for SP that we know about. Also, GABA is the most abundant modulator in the brain, around 30% of all transmitters. Low levels have been associated with panic attacks, anxiety disorders, insomnia and a variety of other problems.
DOPAMINE: I believe this to be the second most important neurotransmitter involved in SP, but I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION. Here's why: High levels of dopamine linked with paranoia, schizophrenia, stress and panic disorders, all of which have high incidences of SP. Also, in animal studies it has been shown that dopamine levels skyrocket after incidences of social defeat. THis dopamine release leads to reducing binding potential of dopamine to its receptors by decreasing number of dopamine receptors. Finnish studies have shown that people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain. Additionally, although there are some exceptions, almost every post I've read where someone tries a dopamine med on its own to combat SP actually experiences increased anxiety. In my own experience, L-tyrosine and selegiline caused additional anxiety and paranoia. Usually dopamine meds are most helpful as adding an activating effect to drugs such as Klonopin, Valium, Neurontin, etc. This all ties in with low levels of GABA, b/c GABA actually inhibits dopamine production, and low levels of GABA lead to higher levels of dopamine.
So basically: Low GABA = High Dopamine levels = downregulation of Dopamine receptors = reduced sensitivity of receptors = low GABA... and the cycle continues.
So to sum it up, it seems to me that GABA dysfunction is the main reason for SP, with poor dopamine transmission due to chronically excess levels in brain as a result of low GABA. Sorry for writing a novel, but it was clogging up my brain! Good luck.
Posted by KrissyP on March 4, 2003, at 23:43:54
In reply to Re: Dopamine agonists, posted by Michael Bell on March 4, 2003, at 23:01:38
WELL DONE MICHAEL:-)
> Daizy, this is what I think about Social Phobia and neurotransmitters. This theory comes from my own experience, discussions in chat rooms and surfing the net for countless hours. I'll take the transmitter systems one at a time.
>
> Serotonin: High levels: linked with harm avoidance and anxiety, including General Anxiety Disorder. Low levels: linked with some forms of depression, obsessions, deviant thoughts and aggression. I don't believe serotonin is a major player in SP, though it's probably involved on some level (maybe levels are slightly high), uin a complex way we don't know about. My main reason for this belief comes from my own experience as well as what I've encountered regarding SSRIs. One common result that I have found across many chatboards and various studies is that SSRIs do NOT help with SP, and in fact often make the symptoms worse. Those that have noticed an effect often say that they feel emotionally numb as a result of taking these medications. My own feeling is that a medication that removes anxiety through dulling of emotions may be "effective" to some degree, but not in a pleasant way. An interesting things about serotonin - it increases when we "freeze" in frightful situations (similar to mind going blank in social settings)
>
> Norepinephrine -- since this is the fight or flight neurotransmitter, it probably also has a role in SP. Caffeine induces panic attacks in people with SP twice as much as people without SP. Also, beta blockers inhibit norepinephrine from reaching receptors, and are useful for people with performance anxiety. However, studies have shown that people with generalized SP actually have similar NE levels to "normal" people. Also, beta blockers are not very effective for generalized SP. Our receptors are probably hypersensitive to NE, so that we have stronger reactions to situations that should only cause minimal stress.
>
> GABA: I believe most of the evidence points to GABA dysfunction as being the primary culprit in SP. Here's why: The two most effective prescription drugs for SP are Klonopin and Nardil. No other drugs come close. KLONOPIN - works by enabling GABA to bind more easily to its receptors. Klonopin sometimes works so well that it causes disinhibition in some patients, the very opposite of SP. NARDIL - one of the older, irreversible MAOIs, it increases the levels of dopamine, serotonin and norepinephrine in the body and brain. However, other MAOIs, such as Parnate, do the same, and are not nearly as effective as Nardil for SP. The difference is Nardil also a powerful inhibitor of the enzyme that breaks down GABA. I believe it is this action on GABA that makes Nardil such an effective tool. The two other substances that I have heard miraculous results about are ALCOHOL and GHB. In my own experience, alcohol is the single most effective substance I have ever tried for SP, too bad it's dangerous! Most researchers attribute the "wellbeing" effect of alcohol to be due to its potentiation of GABA, however there is also some increased dopamine transmission that takes place as well. The effects of GHB are two-fold. First, it increases the effectiveness of GABA for several hours, causing feelings of wellbeing and disinhibition. Over the course of these hours, it also blocks the transmission of dopamine, causing dopamine levels to build up in the brain. Then the user falls asleep and all the built up dopamine is released, causing the user to wake up refreshed and alert. So here we have four drugs, all which act primarily on GABA, and they are the most effective drugs for SP that we know about. Also, GABA is the most abundant modulator in the brain, around 30% of all transmitters. Low levels have been associated with panic attacks, anxiety disorders, insomnia and a variety of other problems.
>
> DOPAMINE: I believe this to be the second most important neurotransmitter involved in SP, but I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION. Here's why: High levels of dopamine linked with paranoia, schizophrenia, stress and panic disorders, all of which have high incidences of SP. Also, in animal studies it has been shown that dopamine levels skyrocket after incidences of social defeat. THis dopamine release leads to reducing binding potential of dopamine to its receptors by decreasing number of dopamine receptors. Finnish studies have shown that people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain. Additionally, although there are some exceptions, almost every post I've read where someone tries a dopamine med on its own to combat SP actually experiences increased anxiety. In my own experience, L-tyrosine and selegiline caused additional anxiety and paranoia. Usually dopamine meds are most helpful as adding an activating effect to drugs such as Klonopin, Valium, Neurontin, etc. This all ties in with low levels of GABA, b/c GABA actually inhibits dopamine production, and low levels of GABA lead to higher levels of dopamine.
>
> So basically: Low GABA = High Dopamine levels = downregulation of Dopamine receptors = reduced sensitivity of receptors = low GABA... and the cycle continues.
>
> So to sum it up, it seems to me that GABA dysfunction is the main reason for SP, with poor dopamine transmission due to chronically excess levels in brain as a result of low GABA. Sorry for writing a novel, but it was clogging up my brain! Good luck.
Posted by KrissyP on March 5, 2003, at 0:16:44
In reply to Re: Dopamine agonists » KrissyP, posted by not exactly on March 4, 2003, at 16:24:14
Thanks:-) FWIW, thank you FYI, I find your site very helpful PRN what a smart guy to have done this:-) BTW, I know most of the icons-but being new and all, there are way easier ways to put words in a post other than spelling them out-your point exactly! And.... I say this:
IDBTD! Meaning I don't beg to differ that your site has been a helpful, educational, and supportive thing in my life the past few days-
THX-Kristen:-)
Thanks for this site Kristen,
>
> > Please? what does FWIW mean LOL:-)
>
> FWIW = "for what it's worth"
>
> BTW, FYI see:
> http://www.dr-bob.org/babble/20010122/msgs/52652.html
> very handy, IMHO
>
> HTH,
> Bob
>
>
Posted by not exactly on March 5, 2003, at 1:57:34
In reply to Re: Dopamine agonists » not exactly, posted by noa on March 4, 2003, at 19:39:11
> I don't see HTH on the list
DYJHIWTH? :-)
HTH = "hope this helps"
see also:
http://www.netlingo.com/emailsh.cfm- Bob
Posted by not exactly on March 5, 2003, at 2:56:34
In reply to Re: Dopamine agonists, posted by Michael Bell on March 4, 2003, at 23:01:38
> ... I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION.
> ... people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain.Fascinating! I really like this theory, because it finally explains some things that never made sense before. For example, it would explain why I responded so well to Mirapex (a dopamine agonist) but after a while it completely "pooped out". Perhaps at first it improved the stimulation of the too-sparse dopamine receptors, but eventually there was a compensatory further downregulation. MAOIs would probably have the same limitation. What sort of drug would enhance dopamine transmission without causing this compensation? A dopamine reuptake inhibitor? A pre-synaptic antagonist? Seems like what is really needed is a med that interferes with the downregulation compensation process.
And how could one reverse the downregulation that had already taken place? Would REDUCING the dopamine levels cause the receptors to become more sensitive? Maybe an antipsychotic/neuroleptic would, in the long term, induce an UPregulation? What do you think?
- Bob
Posted by daizy on March 5, 2003, at 7:47:36
In reply to Re: Dopamine agonists, posted by Michael Bell on March 4, 2003, at 23:01:38
Well Thanx for telling your theory, Its very interesting, you know it seems to make a lot of sense, and explains why some drugs work and others just make it worse!
>"Most researchers attribute the "wellbeing" effect of alcohol to be due to its potentiation of GABA, however there is also some increased dopamine transmission that takes place as well. The effects of GHB are two-fold. First, it increases the effectiveness of GABA for several hours, causing feelings of wellbeing and disinhibition. Over the course of these hours, it also blocks the transmission of dopamine, causing dopamine levels to build up in the brain"
Yes michael, this is true with my experience of taking GHB. I believe this is what happens when taking MDMA also, correct me if Im wrong.
>"Also, GABA is the most abundant modulator in the brain, around 30% of all transmitters. Low levels have been associated with panic attacks, anxiety disorders, insomnia and a variety of other problems"
> "DOPAMINE: I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION. Here's why: High levels of dopamine linked with paranoia, schizophrenia, stress and panic disorders, all of which have high incidences of SP. Also, in animal studies it has been shown that dopamine levels skyrocket after incidences of social defeat. THis dopamine release leads to reducing binding potential of dopamine to its receptors by decreasing number of dopamine receptors. Finnish studies have shown that people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain" Or could this also be because of, in my instance, taking drugs that then increased dopamine?>"So basically: Low GABA = High Dopamine levels = downregulation of Dopamine receptors = reduced sensitivity of receptors = low GABA... and the cycle continues.
>
> So to sum it up, it seems to me that GABA dysfunction is the main reason for SP, with poor dopamine transmission due to chronically excess levels in brain as a result of low GABA"
So does this mean that to combat SP and anxiety, you need a drug that primarily increases GABA, and then adding an SSRI or SNRI to increase the levels of others?I think I have understood!
Posted by Michael Bell on March 5, 2003, at 10:59:53
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 5, 2003, at 2:56:34
> > ... I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION.
> > ... people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain.
>
> Fascinating! I really like this theory, because it finally explains some things that never made sense before. For example, it would explain why I responded so well to Mirapex (a dopamine agonist) but after a while it completely "pooped out". Perhaps at first it improved the stimulation of the too-sparse dopamine receptors, but eventually there was a compensatory further downregulation. MAOIs would probably have the same limitation. What sort of drug would enhance dopamine transmission without causing this compensation? A dopamine reuptake inhibitor? A pre-synaptic antagonist? Seems like what is really needed is a med that interferes with the downregulation compensation process.
>
> And how could one reverse the downregulation that had already taken place? Would REDUCING the dopamine levels cause the receptors to become more sensitive? Maybe an antipsychotic/neuroleptic would, in the long term, induce an UPregulation? What do you think?
>
> - Bob
>Bob, it's so interesting what you've added to the thread regarding your experiences. I also believe that when we take drugs that increase dopamine, this allows the reduced number of receptors to be stimulated by the increased dopamine - for a while. Then the brain registers this excess dopamine, and further downregulates the number of receptors, hence the poop-out effect. I too am trying to find out about drugs that effect dopamine transmission itself and not just increase overall dopamine levels.
Regarding upregulation - interestingly, in people with Parkinson's disease, studies have shown that as the number of dopamine cells gets lower, the brain upregulates the number of receptors to compensate. However, eventually the number of cells get so low (80% reduction) that even having a higher number of receptors doesn't help. So there is probably a way to increase the number of dopamine receptors, but safety is a big issue.
Posted by jumpy on March 5, 2003, at 11:38:17
In reply to Re: Dopamine agonists, posted by Michael Bell on March 5, 2003, at 10:59:53
> Bob, it's so interesting what you've added to the thread regarding your experiences. I also believe that when we take drugs that increase dopamine, this allows the reduced number of receptors to be stimulated by the increased dopamine - for a while. Then the brain registers this excess dopamine, and further downregulates the number of receptors, hence the poop-out effect. I too am trying to find out about drugs that effect dopamine transmission itself and not just increase overall dopamine levels.
>
> Regarding upregulation - interestingly, in people with Parkinson's disease, studies have shown that as the number of dopamine cells gets lower, the brain upregulates the number of receptors to compensate. However, eventually the number of cells get so low (80% reduction) that even having a higher number of receptors doesn't help. So there is probably a way to increase the number of dopamine receptors, but safety is a big issue.Hey Michael,
Very interesting. So with nardil, is the benefits solely in the increase in GABA levels and the increases in dopamine/serotonin/norepi are actually detrimental? I am on nardil and klonopin ... should I just taper off the nardil and increase the klonopin if increasing GABA is the sole goal (and nardil might be hurting with the serotonin/dopamine/norepi effects)?
Thanks.
Jumpy
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