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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by karaS on October 24, 2004, at 5:09:36
Todd,
Thought you might like to see this abstract which seems to confirm what you've been saying. Here's the key sentence from it:
"MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors."
Here's the link:
http://www.chocolate.org/peadep.htm
Kara
Posted by Kristel on October 24, 2004, at 5:47:28
In reply to MAOIs decrease density of DA receptors- KingVultan, posted by karaS on October 24, 2004, at 5:09:36
> Todd,
>
> Thought you might like to see this abstract which seems to confirm what you've been saying. Here's the key sentence from it:
>
> "MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors."
>
> Here's the link:
>
> http://www.chocolate.org/peadep.htm
>
> KaraAnd that is a negative thing to happen ?!!
In fact the opposite might be true. Decrease in receptos density mean down-regulation which is thought of as the anti-depressant mechanism of these drugs. Decrease in density means increase in sensitivity of the receptors.
Posted by King Vultan on October 24, 2004, at 10:28:13
In reply to Re: MAOIs decrease density of DA receptors- KingVultan, posted by Kristel on October 24, 2004, at 5:47:28
> > Todd,
> >
> > Thought you might like to see this abstract which seems to confirm what you've been saying. Here's the key sentence from it:
> >
> > "MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors."
> >
> > Here's the link:
> >
> > http://www.chocolate.org/peadep.htm
> >
> > Kara
>
> And that is a negative thing to happen ?!!
>
> In fact the opposite might be true. Decrease in receptos density mean down-regulation which is thought of as the anti-depressant mechanism of these drugs. Decrease in density means increase in sensitivity of the receptors.
No, decreasing density is the same as reducing sensitivity; hypersensitivity implies that there are many more receptors than are ideal in a particular area. Downregulation decreases sensitivity by reducing the number of receptors.Be that as it may, the abstract is interesting, but I don't know enough about dopamine receptors to come to any firm conclusions myself. I was aware that phenylethylamine is a classic MAO-B substrate, which is one of the reasons behind chocolate appearing on some of the "Do not eat" lists for MAOI patients (PEA has been called the "chocolate amphetamine"). Inhibiting MAO-B as do the older MAOIs--and as selegiline does, as well--does increase PEA levels, and there appears to be at least a possibility that there may be some therapeutic benefits from this.
Todd
Posted by Larry Hoover on October 24, 2004, at 11:12:52
In reply to Re: MAOIs decrease density of DA receptors- KaraS » Kristel, posted by King Vultan on October 24, 2004, at 10:28:13
> Be that as it may, the abstract is interesting, but I don't know enough about dopamine receptors to come to any firm conclusions myself. I was aware that phenylethylamine is a classic MAO-B substrate, which is one of the reasons behind chocolate appearing on some of the "Do not eat" lists for MAOI patients (PEA has been called the "chocolate amphetamine"). Inhibiting MAO-B as do the older MAOIs--and as selegiline does, as well--does increase PEA levels, and there appears to be at least a possibility that there may be some therapeutic benefits from this.
>
> ToddI'd like to lend support to the idea that MAO-B inhibition has therapeutic benefits. I'm currently experimenting with low-dose oral selegiline, and I'm finding that my optimal intake might lie at only 7.5 mg/day....still tweaking though. I also find that oral DLPA potentiates the effect considerably, lending credence to the PEA mechanism.
My cognitive function continues to improve, on a day to day basis. I believe that my physical endurance might be increasing, but more slowly. I don't wish to place expectations on myself, but it seems to be the case.
I think the classical focus on the Big Three neurotransmitters is very short-sighted. Without getting too lost in semantics, perhaps PEA and taurine and GABA and phosphatidylserine and others might best be called neuromodulators....but in any case......
Lar
Posted by Kristel on October 24, 2004, at 11:24:53
In reply to Re: MAOIs decrease density of DA receptors- KaraS » King Vultan, posted by Larry Hoover on October 24, 2004, at 11:12:52
> > Be that as it may, the abstract is interesting, but I don't know enough about dopamine receptors to come to any firm conclusions myself. I was aware that phenylethylamine is a classic MAO-B substrate, which is one of the reasons behind chocolate appearing on some of the "Do not eat" lists for MAOI patients (PEA has been called the "chocolate amphetamine"). Inhibiting MAO-B as do the older MAOIs--and as selegiline does, as well--does increase PEA levels, and there appears to be at least a possibility that there may be some therapeutic benefits from this.
> >
> > Todd
>
> I'd like to lend support to the idea that MAO-B inhibition has therapeutic benefits. I'm currently experimenting with low-dose oral selegiline, and I'm finding that my optimal intake might lie at only 7.5 mg/day....still tweaking though. I also find that oral DLPA potentiates the effect considerably, lending credence to the PEA mechanism.
>
> My cognitive function continues to improve, on a day to day basis. I believe that my physical endurance might be increasing, but more slowly. I don't wish to place expectations on myself, but it seems to be the case.
>
> I think the classical focus on the Big Three neurotransmitters is very short-sighted. Without getting too lost in semantics, perhaps PEA and taurine and GABA and phosphatidylserine and others might best be called neuromodulators....but in any case......
>
> Lar
>How much DLPA are you taking ?!
Posted by karaS on October 24, 2004, at 15:39:58
In reply to Re: MAOIs decrease density of DA receptors- KaraS » Kristel, posted by King Vultan on October 24, 2004, at 10:28:13
> > > Todd,
> > >
> > > Thought you might like to see this abstract which seems to confirm what you've been saying. Here's the key sentence from it:
> > >
> > > "MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors."
> > >
> > > Here's the link:
> > >
> > > http://www.chocolate.org/peadep.htm
> > >
> > > Kara
> >
> > And that is a negative thing to happen ?!!
> >
> > In fact the opposite might be true. Decrease in receptos density mean down-regulation which is thought of as the anti-depressant mechanism of these drugs. Decrease in density means increase in sensitivity of the receptors.
>
>
> No, decreasing density is the same as reducing sensitivity; hypersensitivity implies that there are many more receptors than are ideal in a particular area. Downregulation decreases sensitivity by reducing the number of receptors.
>
> Be that as it may, the abstract is interesting, but I don't know enough about dopamine receptors to come to any firm conclusions myself. I was aware that phenylethylamine is a classic MAO-B substrate, which is one of the reasons behind chocolate appearing on some of the "Do not eat" lists for MAOI patients (PEA has been called the "chocolate amphetamine"). Inhibiting MAO-B as do the older MAOIs--and as selegiline does, as well--does increase PEA levels, and there appears to be at least a possibility that there may be some therapeutic benefits from this.
>
> ToddTodd,
If I read the abstract correctly, then the MAOI phenelzine was able to decrease density of D1 and D2 while selegiline was only able to decrease density of D1.I'm thinking that I should be trying an MAOI now.
I think that my dopamine autoreceptor problem is a recent one (though I've suffered from depression for almost 30 years). The reason I say this is because I've only recently, within the last couple of years, gotten tired from exercising. It's not a fatigue that happens when I exercise. It's an hour or two later that I want to go to sleep. I had entertained the idea that it was an adrenal problem but I feel fine while exercising and shortly afterwards. I'm convinced now that the exercise boosts dopamine and then a while later (because of the DA receptors), I need to go to sleep.
Then I'm left with why this has happened to me now. It could be that long term CFS has finally done this to me (per Dr. Jay Goldstein's theory) or possibly long-term SSRI usage. The latter also makes me question whether Cymbalta is a good medication for me now.
Kara
Posted by King Vultan on October 25, 2004, at 7:59:30
In reply to Re: MAOIs decrease density of DA receptors » King Vultan, posted by karaS on October 24, 2004, at 15:39:58
>
> Todd,
> If I read the abstract correctly, then the MAOI phenelzine was able to decrease density of D1 and D2 while selegiline was only able to decrease density of D1.
>
> I'm thinking that I should be trying an MAOI now.
>
> I think that my dopamine autoreceptor problem is a recent one (though I've suffered from depression for almost 30 years). The reason I say this is because I've only recently, within the last couple of years, gotten tired from exercising. It's not a fatigue that happens when I exercise. It's an hour or two later that I want to go to sleep. I had entertained the idea that it was an adrenal problem but I feel fine while exercising and shortly afterwards. I'm convinced now that the exercise boosts dopamine and then a while later (because of the DA receptors), I need to go to sleep.
>
> Then I'm left with why this has happened to me now. It could be that long term CFS has finally done this to me (per Dr. Jay Goldstein's theory) or possibly long-term SSRI usage. The latter also makes me question whether Cymbalta is a good medication for me now.
>
> Kara
>Actually, I think it said PEA (phenylethylamine) reduced D1 receptor density, and MAOIs decreased both D1 and D2. So there should not be a big difference in that regard between phenelzine and selegiline because both are MAOIs. I'm not sure what the best course is for you. I think I may have a dopamine autoreceptor problem also, but it seems clear that mine is manifesting itself differently than yours, probably because mine is in some other area of the brain and not necessarily in the nucleus accumbens.
Todd
Posted by karaS on October 25, 2004, at 13:30:27
In reply to Re: MAOIs decrease density of DA receptors » karaS, posted by King Vultan on October 25, 2004, at 7:59:30
>
> >
> > Todd,
> > If I read the abstract correctly, then the MAOI phenelzine was able to decrease density of D1 and D2 while selegiline was only able to decrease density of D1.
> >
> > I'm thinking that I should be trying an MAOI now.
> >
> > I think that my dopamine autoreceptor problem is a recent one (though I've suffered from depression for almost 30 years). The reason I say this is because I've only recently, within the last couple of years, gotten tired from exercising. It's not a fatigue that happens when I exercise. It's an hour or two later that I want to go to sleep. I had entertained the idea that it was an adrenal problem but I feel fine while exercising and shortly afterwards. I'm convinced now that the exercise boosts dopamine and then a while later (because of the DA receptors), I need to go to sleep.
> >
> > Then I'm left with why this has happened to me now. It could be that long term CFS has finally done this to me (per Dr. Jay Goldstein's theory) or possibly long-term SSRI usage. The latter also makes me question whether Cymbalta is a good medication for me now.
> >
> > Kara
> >
>
> Actually, I think it said PEA (phenylethylamine) reduced D1 receptor density, and MAOIs decreased both D1 and D2. So there should not be a big difference in that regard between phenelzine and selegiline because both are MAOIs. I'm not sure what the best course is for you. I think I may have a dopamine autoreceptor problem also, but it seems clear that mine is manifesting itself differently than yours, probably because mine is in some other area of the brain and not necessarily in the nucleus accumbens.
>
> Todd
Ok, if it's the PEA they were referring to then the selegiline should also do the trick. (I'm assuming it would have to be taken at nonselective dosage though.)I'm sure you know what your condition is between your research and your experience on various medications. I questioned you earlier about it so that I could understand from your response how we could have similar problems yet different symptoms. I find it hard to pin things down when there are several types of dopamine receptors and they occur in different areas of the brain. For instance, given that I have the hypersensitive DA receptors, you would expect that I would be anhedonic - but most of the time I'm not. I have no motivation to speak of, yet I'm usually able to find some joy in every day living. I wonder if it's possible through enough research to figure out which DA receptors one has a problem with and in which area(s) of the brain the problem exists. It probably carries no weight in terms of being able to correct the problem as the drugs we have now are not specific enough, are they?
Kara
Posted by SFY on October 25, 2004, at 21:24:48
In reply to Re: MAOIs decrease density of DA receptors » King Vultan, posted by karaS on October 25, 2004, at 13:30:27
> Ok, if it's the PEA they were referring to then the selegiline should also do the trick. (I'm assuming it would have to be taken at nonselective dosage though.)
>
> I'm sure you know what your condition is between your research and your experience on various medications. I questioned you earlier about it so that I could understand from your response how we could have similar problems yet different symptoms. I find it hard to pin things down when there are several types of dopamine receptors and they occur in different areas of the brain. For instance, given that I have the hypersensitive DA receptors, you would expect that I would be anhedonic - but most of the time I'm not. I have no motivation to speak of, yet I'm usually able to find some joy in every day living. I wonder if it's possible through enough research to figure out which DA receptors one has a problem with and in which area(s) of the brain the problem exists. It probably carries no weight in terms of being able to correct the problem as the drugs we have now are not specific enough, are they?
>
> Kara
>It would be nice if someone with more understanding had some way of breaking this down and at least narrowing the field of what to try. I'm anhedonic and undermotivated but selegiline (at least at the selective dosage) has no effect on me (except for the paradoxical loss of libido and sexual dysfunction). And I'm not sure what it all means.
Posted by karaS on October 25, 2004, at 22:03:12
In reply to Re: MAOIs decrease density of DA receptors » karaS, posted by SFY on October 25, 2004, at 21:24:48
> > Ok, if it's the PEA they were referring to then the selegiline should also do the trick. (I'm assuming it would have to be taken at nonselective dosage though.)
> >
> > I'm sure you know what your condition is between your research and your experience on various medications. I questioned you earlier about it so that I could understand from your response how we could have similar problems yet different symptoms. I find it hard to pin things down when there are several types of dopamine receptors and they occur in different areas of the brain. For instance, given that I have the hypersensitive DA receptors, you would expect that I would be anhedonic - but most of the time I'm not. I have no motivation to speak of, yet I'm usually able to find some joy in every day living. I wonder if it's possible through enough research to figure out which DA receptors one has a problem with and in which area(s) of the brain the problem exists. It probably carries no weight in terms of being able to correct the problem as the drugs we have now are not specific enough, are they?
> >
> > Kara
> >
>
> It would be nice if someone with more understanding had some way of breaking this down and at least narrowing the field of what to try. I'm anhedonic and undermotivated but selegiline (at least at the selective dosage) has no effect on me (except for the paradoxical loss of libido and sexual dysfunction). And I'm not sure what it all means.
>It would be nice if we had this information to help us with all aspects of antidepressant choice. Maybe a couple hundred years from now we will (sigh).
Posted by cybercafe on October 26, 2004, at 6:40:31
In reply to Re: MAOIs decrease density of DA receptors » King Vultan, posted by karaS on October 25, 2004, at 13:30:27
> >
> > >
> > > Todd,
> > > If I read the abstract correctly, then the MAOI phenelzine was able to decrease density of D1 and D2 while selegiline was only able to decrease density of D1.
> > >
> > > I'm thinking that I should be trying an MAOI now.
> > >
> > > I think that my dopamine autoreceptor problem is a recent one (though I've suffered from depression for almost 30 years). The reason I say this is because I've only recently, within the last couple of years, gotten tired from exercising. It's not a fatigue that happens when I exercise. It's an hour or two later that I want to go to sleep. I had entertained the idea that it was an adrenal problem but I feel fine while exercising and shortly afterwards. I'm convinced now that the exercise boosts dopamine and then a while later (because of the DA receptors), I need to go to sleep.
> > >
> > > Then I'm left with why this has happened to me now. It could be that long term CFS has finally done this to me (per Dr. Jay Goldstein's theory) or possibly long-term SSRI usage. The latter also makes me question whether Cymbalta is a good medication for me now.
> > >
> > > Kara
> > >
> >
> > Actually, I think it said PEA (phenylethylamine) reduced D1 receptor density, and MAOIs decreased both D1 and D2. So there should not be a big difference in that regard between phenelzine and selegiline because both are MAOIs. I'm not sure what the best course is for you. I think I may have a dopamine autoreceptor problem also, but it seems clear that mine is manifesting itself differently than yours, probably because mine is in some other area of the brain and not necessarily in the nucleus accumbens.
> >
> > Todd
>
>
> Ok, if it's the PEA they were referring to then the selegiline should also do the trick. (I'm assuming it would have to be taken at nonselective dosage though.)
>
> I'm sure you know what your condition is between your research and your experience on various medications. I questioned you earlier about it so that I could understand from your response how we could have similar problems yet different symptoms. I find it hard to pin things down when there are several types of dopamine receptors and they occur in different areas of the brain. For instance, given that I have the hypersensitive DA receptors, you would expect that I would be anhedonic - but most of the time I'm not. I have no motivation to speak of, yet I'm usually able to find some joy in every day living. I wonder if it's possible through enough research to figure out which DA receptors one has a problem with and in which area(s) of the brain the problem exists. It probably carries no weight in terms of being able to correct the problem as the drugs we have now are not specific enough, are they?
>
> Kara
>
>
>Hmm.. Motivation is a strange thing. I know antipsychotics that decrease firing of dopamine receptors can cause akathisia (D2 in substantia nigra or something? ug it's been a long time), which I think, when not very severe, is the same as, or very similiar to, what we call "motivation". That has been my experience on abilify anyway. I just don't understand people who procrastinate anymore. On the other hand, antipsychotics also tend to cause anhedonia (D4 in nucleus accumbens? I believe this is the target of stimulants, which seem to decrease anhedonia).
Posted by karaS on October 26, 2004, at 15:39:59
In reply to Re: MAOIs decrease density of DA receptors, posted by cybercafe on October 26, 2004, at 6:40:31
> > >
> > > >
> > > > Todd,
> > > > If I read the abstract correctly, then the MAOI phenelzine was able to decrease density of D1 and D2 while selegiline was only able to decrease density of D1.
> > > >
> > > > I'm thinking that I should be trying an MAOI now.
> > > >
> > > > I think that my dopamine autoreceptor problem is a recent one (though I've suffered from depression for almost 30 years). The reason I say this is because I've only recently, within the last couple of years, gotten tired from exercising. It's not a fatigue that happens when I exercise. It's an hour or two later that I want to go to sleep. I had entertained the idea that it was an adrenal problem but I feel fine while exercising and shortly afterwards. I'm convinced now that the exercise boosts dopamine and then a while later (because of the DA receptors), I need to go to sleep.
> > > >
> > > > Then I'm left with why this has happened to me now. It could be that long term CFS has finally done this to me (per Dr. Jay Goldstein's theory) or possibly long-term SSRI usage. The latter also makes me question whether Cymbalta is a good medication for me now.
> > > >
> > > > Kara
> > > >
> > >
> > > Actually, I think it said PEA (phenylethylamine) reduced D1 receptor density, and MAOIs decreased both D1 and D2. So there should not be a big difference in that regard between phenelzine and selegiline because both are MAOIs. I'm not sure what the best course is for you. I think I may have a dopamine autoreceptor problem also, but it seems clear that mine is manifesting itself differently than yours, probably because mine is in some other area of the brain and not necessarily in the nucleus accumbens.
> > >
> > > Todd
> >
> >
> > Ok, if it's the PEA they were referring to then the selegiline should also do the trick. (I'm assuming it would have to be taken at nonselective dosage though.)
> >
> > I'm sure you know what your condition is between your research and your experience on various medications. I questioned you earlier about it so that I could understand from your response how we could have similar problems yet different symptoms. I find it hard to pin things down when there are several types of dopamine receptors and they occur in different areas of the brain. For instance, given that I have the hypersensitive DA receptors, you would expect that I would be anhedonic - but most of the time I'm not. I have no motivation to speak of, yet I'm usually able to find some joy in every day living. I wonder if it's possible through enough research to figure out which DA receptors one has a problem with and in which area(s) of the brain the problem exists. It probably carries no weight in terms of being able to correct the problem as the drugs we have now are not specific enough, are they?
> >
> > Kara
> >
> >
> >
>
> Hmm.. Motivation is a strange thing. I know antipsychotics that decrease firing of dopamine receptors can cause akathisia (D2 in substantia nigra or something? ug it's been a long time), which I think, when not very severe, is the same as, or very similiar to, what we call "motivation". That has been my experience on abilify anyway. I just don't understand people who procrastinate anymore. On the other hand, antipsychotics also tend to cause anhedonia (D4 in nucleus accumbens? I believe this is the target of stimulants, which seem to decrease anhedonia).
Maybe we're further along in this research than I'm giving us credit for.I don't understand what akathisia has to do with motivation?
This is the end of the thread.
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