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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by JohnX2 on November 1, 2001, at 3:41:12
Looking for info on dopamine receptor
supersensitivy articles/background.
Experts out there?Have read interesting theories on how
psychostimulants can cause dysfunctional
pre/post synaptic dopamine receptor ratios,
sensitivity,feeback inhibition.
I also believe this could be a source of med-poop out.
Also believe that it can be reversed
(possibly using an NMDA antagonist
+ a dopamine agonist/antagonist). Just a hunch...-john
Posted by JGalt on November 3, 2001, at 22:38:49
In reply to dopamine receptor supersensitivy, posted by JohnX2 on November 1, 2001, at 3:41:12
John it seems you are the expert at your own question here after reading through some of the research you've already dug up on this...also seems to me that there's more than just a hunch to the NMDA receptor theory. Give me a guinea pig outfit, adderal, memantine, and directions to the nearest observational facility and I think we'll have a positive on the hypothesis.
Posted by JohnX2 on November 4, 2001, at 1:27:29
In reply to Re: dopamine receptor supersensitivy, posted by JGalt on November 3, 2001, at 22:38:49
> John it seems you are the expert at your own question here after reading through some of the research you've already dug up on this...also seems to me that there's more than just a hunch to the NMDA receptor theory. Give me a guinea pig outfit, adderal, memantine, and directions to the nearest observational facility and I think we'll have a positive on the hypothesis.
Halloween was 3 days ago, don't you think you'd
look a bit silly walking around in a guinea
pig outfit?-john
Posted by Collette on November 4, 2001, at 9:38:59
In reply to Re: dopamine receptor supersensitivy » JGalt, posted by JohnX2 on November 4, 2001, at 1:27:29
> > John it seems you are the expert at your own question here after reading through some of the research you've already dug up on this...also seems to me that there's more than just a hunch to the NMDA receptor theory. Give me a guinea pig outfit, adderal, memantine, and directions to the nearest observational facility and I think we'll have a positive on the hypothesis.
What are other drugs that do this, besides adderal and memantine? Is Provigil one? Thanks, Collette
Posted by SLS on November 4, 2001, at 12:28:16
In reply to dopamine receptor supersensitivy, posted by JohnX2 on November 1, 2001, at 3:41:12
Hi John (and others)
> Looking for info on dopamine receptor
> supersensitivy articles/background.
> Experts out there?Not me.
> Have read interesting theories on how
> psychostimulants can cause dysfunctional
> pre/post synaptic dopamine receptor ratios,
> sensitivity,feeback inhibition.
> I also believe this could be a source of med-poop out.
> Also believe that it can be reversed
> (possibly using an NMDA antagonist
> + a dopamine agonist/antagonist). Just a hunch...
>
> -john
Check-out ibogaine:http://www.med.nyu.edu/Psych/ibogaineconf/objectives.html
It is a NMDA receptor antagonist that has quite a bit of history involving use for the treatment of drug addiction. It seems to prevent or reverse neuroadaptive changes (eg. receptor sensitivity) resulting from drug exposure. It also does a bunch of other things that I'm sure you'll have fun researching.
- Scott
Posted by JohnX2 on November 4, 2001, at 13:49:24
In reply to Re: dopamine receptor supersensitivy » JohnX2, posted by SLS on November 4, 2001, at 12:28:16
Thanks Scott,I have come across Ibogaine references.
It is definately interesting.Any luck with your treatment path?
Are you steady with your current
meds?-john
> Hi John (and others)
>
> > Looking for info on dopamine receptor
> > supersensitivy articles/background.
> > Experts out there?
>
> Not me.
>
> > Have read interesting theories on how
> > psychostimulants can cause dysfunctional
> > pre/post synaptic dopamine receptor ratios,
> > sensitivity,feeback inhibition.
> > I also believe this could be a source of med-poop out.
> > Also believe that it can be reversed
> > (possibly using an NMDA antagonist
> > + a dopamine agonist/antagonist). Just a hunch...
> >
> > -john
>
>
> Check-out ibogaine:
>
> http://www.med.nyu.edu/Psych/ibogaineconf/objectives.html
>
> It is a NMDA receptor antagonist that has quite a bit of history involving use for the treatment of drug addiction. It seems to prevent or reverse neuroadaptive changes (eg. receptor sensitivity) resulting from drug exposure. It also does a bunch of other things that I'm sure you'll have fun researching.
>
>
> - Scott
Posted by SLS on November 6, 2001, at 11:40:09
In reply to Re: dopamine receptor supersensitivy » SLS, posted by JohnX2 on November 4, 2001, at 13:49:24
> Any luck with your treatment path?
> Are you steady with your current
> meds?
Things are pretty screwy.1. I tried unsuccessfully to reduce my dosage of Lamictal. It seems I need 300mg. to receive benefit from it. However, I am suspicious that it is responsible for some cognitive blunting and memory impairments. It might also be responsible for my inability to take moderate dosages of atypical neuroleptics without developing unacceptable cognitive disturbances. Otherwise, these drugs do help me. Lamictal was definitely responsible for a similar state when I raised my dosage of Parnate above 40mg. This state disappeared upon dosage reduction and re-emerged upon increase. When I more recently reduced the dosage of Lamictal to 200mg., I felt as if some of my "old" familiar self reappeared. This was a good thing, I think. Maybe I can finesse the dosage around 250mg.
2. Adding Effexor to nortriptyline 100mg. produces a "brain-fog" that does not seem to be mitigating with time. Otherwise, it probably helps a bit.
3. No single dosage of nortriptyline seems to work steadily. It does produce a mild and necessary improvement at times, but I must keep changing the dosage to maintain it. Before adding Effexor, 100mg. of nortriptyline was pretty good, but still somewhat variable. I lost all benefit at dosages of 75mg. and 125mg. Now, any therapeutic window that exists lies between 25mg. and 50mg. I become severely depressed at 100mg. Perhaps this is due to a pharmacokinetic interaction as both Effexor and nortriptyline are substrates of cytochrome P450 2D6. I might go for a blood-level, but that might only be of heuristic value.
4. Adding Remeron exacerbated my depression after only one 7.5mg. dose. I didn't take a second. My doctor wants for me to try it again once my Lamictal experiment is concluded and I am stabilized on a steady regimen. I might not find such a stable regimen unless I switch from nortriptyline to another tricyclic. Imipramine would be my first choice for efficacy, but it causes me to gain weight and produces some memory impairment and possibly other cognitive disturbances. Although desipramine is milder with regard to these side effects, its antidepressant effects are inferior.
5. The use of imipramine, but not desipramine, makes it very difficult to add Nardil. Since Nardil is probably my best choice to use in place of Effexor, this becomes a real obstacle. Two years ago, I tried to add Nardil to imipramine 300mg. When I reached 45mg., I could not stand up due to hypotension and I had to crawl to get from place to place. It was almost impossible to initiate urination. I was scared that I would have to go to the hospital to be catheterized.
6. My situation pretty much sucks. I like challenges, but...
Thanks for asking.
:-)
- Scott
Posted by Noa on November 6, 2001, at 17:23:38
In reply to Re: dopamine receptor supersensitivy » JohnX2, posted by SLS on November 4, 2001, at 12:28:16
One thing I did once hear was that some research was done, I'd say about 10 years ago, using animal models, that showed that repeated exposure and then withdrawal of stimulants (ie, dramatic spiking up and down) did lead to increased sensitivity to the stimulants. Sorry I have no specific citations--I'll try to find it.
Posted by JohnX2 on November 6, 2001, at 23:02:48
In reply to Re: dopamine receptor supersensitivy » JohnX2, posted by SLS on November 6, 2001, at 11:40:09
Dude my heart bleeds for you.I do remember people talking about taking
Flomax for urinary retention issues on
Reboxetine. The thing about postural hypotension
causing you to crawl is pretty scary. I had
a couple times when I felt like my heart was
hardly beating and my blood pressure dropped
and I thought I would go into a coma, scary
stuff.Are you experiencing major depression, cyclothymia,
inbetween major depression/dysthymia depending
on the med combo and day of week etc? How would
you describe your current state beyond it sucking?-john
>
> > Any luck with your treatment path?
> > Are you steady with your current
> > meds?
>
>
> Things are pretty screwy.
>
> 1. I tried unsuccessfully to reduce my dosage of Lamictal. It seems I need 300mg. to receive benefit from it. However, I am suspicious that it is responsible for some cognitive blunting and memory impairments. It might also be responsible for my inability to take moderate dosages of atypical neuroleptics without developing unacceptable cognitive disturbances. Otherwise, these drugs do help me. Lamictal was definitely responsible for a similar state when I raised my dosage of Parnate above 40mg. This state disappeared upon dosage reduction and re-emerged upon increase. When I more recently reduced the dosage of Lamictal to 200mg., I felt as if some of my "old" familiar self reappeared. This was a good thing, I think. Maybe I can finesse the dosage around 250mg.
>
> 2. Adding Effexor to nortriptyline 100mg. produces a "brain-fog" that does not seem to be mitigating with time. Otherwise, it probably helps a bit.
>
> 3. No single dosage of nortriptyline seems to work steadily. It does produce a mild and necessary improvement at times, but I must keep changing the dosage to maintain it. Before adding Effexor, 100mg. of nortriptyline was pretty good, but still somewhat variable. I lost all benefit at dosages of 75mg. and 125mg. Now, any therapeutic window that exists lies between 25mg. and 50mg. I become severely depressed at 100mg. Perhaps this is due to a pharmacokinetic interaction as both Effexor and nortriptyline are substrates of cytochrome P450 2D6. I might go for a blood-level, but that might only be of heuristic value.
>
> 4. Adding Remeron exacerbated my depression after only one 7.5mg. dose. I didn't take a second. My doctor wants for me to try it again once my Lamictal experiment is concluded and I am stabilized on a steady regimen. I might not find such a stable regimen unless I switch from nortriptyline to another tricyclic. Imipramine would be my first choice for efficacy, but it causes me to gain weight and produces some memory impairment and possibly other cognitive disturbances. Although desipramine is milder with regard to these side effects, its antidepressant effects are inferior.
>
> 5. The use of imipramine, but not desipramine, makes it very difficult to add Nardil. Since Nardil is probably my best choice to use in place of Effexor, this becomes a real obstacle. Two years ago, I tried to add Nardil to imipramine 300mg. When I reached 45mg., I could not stand up due to hypotension and I had to crawl to get from place to place. It was almost impossible to initiate urination. I was scared that I would have to go to the hospital to be catheterized.
>
> 6. My situation pretty much sucks. I like challenges, but...
>
> Thanks for asking.
>
> :-)
>
> - Scott
This is the end of the thread.
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