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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 13 to 37 of 37. Go back in thread:
Posted by gardenergirl on October 11, 2004, at 10:49:28
In reply to Re: Exercise problems with Nardil or Parnate? » gardenergirl, posted by King Vultan on October 11, 2004, at 8:09:43
> Parnate seems much better as far as both exercising and weight gain.
>
> ToddInteresting, I asked my pdoc about switching to Parnate as I thought it might be better for me as far as weight gain goes. She looked some stuff up and said that Nardil was preferred if weight gain was an issue. ?????? This seems to go against everything I've seen on this board.
gg
Posted by maddog on October 11, 2004, at 12:03:22
In reply to Re: Exercise problems with Nardil or Parnate? » King Vultan, posted by gardenergirl on October 11, 2004, at 10:49:28
> > Parnate seems much better as far as both exercising and weight gain.
> >
> > Todd
>
> Interesting, I asked my pdoc about switching to Parnate as I thought it might be better for me as far as weight gain goes. She looked some stuff up and said that Nardil was preferred if weight gain was an issue. ?????? This seems to go against everything I've seen on this board.
>
> gg
>Hi GG,
That seems odd to me too. I've only heard about weight gain problems with Nardil, not Parnate.
When I started Nardil I thought that I could combat urges for sweets. Boy, was I wrong! I've been eating chocolate like crazy. I've got to stop (but it tastes so good) and with Halloweén coming up every drugstore is full of bags of cheap chocolate. Ack!
In any case, I'm going to press on with the exercise and hope I can regulate myself better. I too sweat like crazy and just feel weak. Someone on the board mentioned increasing salt intake which helps increase BP. However, I know the real problem is my calorie intake. I can work off 400-600 calories in an exercise session but then turn around and eat a bag of chocolate with 800 calories. Got to control the eating.
maddog
Posted by King Vultan on October 11, 2004, at 12:04:48
In reply to Re: Exercise problems with Nardil or Parnate? » King Vultan, posted by gardenergirl on October 11, 2004, at 10:49:28
>
> Interesting, I asked my pdoc about switching to Parnate as I thought it might be better for me as far as weight gain goes. She looked some stuff up and said that Nardil was preferred if weight gain was an issue. ?????? This seems to go against everything I've seen on this board.
>
> gg
>Right, it's exactly backwards of everything I've ever read, here and elsewhere.
Todd
Posted by gardenergirl on October 11, 2004, at 12:25:11
In reply to Re: Exercise problems with Nardil or Parnate? » gardenergirl, posted by King Vultan on October 11, 2004, at 12:04:48
I'm beginning to wonder about my pdoc. She also said that a symptom I have had in the last six months or so (a strange gurgling sound in my skull) is a psychotic symptom associated with more severe depression. If that's true, how come I have it when my depression is moderate at worst and mild right now? Rather I think it's something related to the ear/nose/throat.
Anyway, thanks for the info.
gg
Posted by iris2 on October 13, 2004, at 10:17:23
In reply to Exercise problems with Nardil or Parnate?, posted by gardenergirl on October 11, 2004, at 0:02:35
My experience with Parnate is that I had more motivation to exorcise and lost weight due to no being so interested in eating. My observation is that people on Nardil tend to gain weight and of course that would make it more difficult to exorcise and you would sweat more.
However I do know that Nardil did nothing for me and that my friend did well on Nardil and Parnate had no effect on her. She did gain a lot of weight though.
I also had a lot of trouble with hypotention so when I exorcised on Parnate or Marplan I often passed out.
irene
Posted by karaS on October 16, 2004, at 14:52:32
In reply to Re: Parnate Experience » karaS, posted by King Vultan on October 11, 2004, at 9:36:12
> I don't think there's necessarily anything terribly wrong with my NE system because I responded to desipramine and protriptyline exactly as one is supposed to, and these are selective NE reuptake inhibitors. I know I do have hypersensitive alpha-1 adrenergic receptors, but I'm not sure how much this really matters. I suppose it could have something to do with the strange effect the Provigil had on me, though.
>
> As far as the hypersensitive dopamine autoreceptors, based on my anhedonia, low libido, ADD symptoms, etc., my dopamine system does appear to operate at a chronically low level, and considering my reactions to various drugs, it's as good a hypothesis as any. I'm not an MD or a PhD researcher, but I question the notion of not being able to downregulate dopamine autoreceptors. I don't quite understand why the heck that would be. Also, keep in mind that two people with the same general condition may have it expressed in different ways or differ in some intricacies. There are four separate dopamine pathways in the brain, and these are interconnected with a myriad of other stuff. It does not seem reasonable to expect that everyone with hypersensitive dopamine autoreceptors would react to every medication the same way; although, one would hope there might be some similarities. From what you've said, you do appear to be more likely to have hypersensitive dopamine autoreceptors than I do.
>
> ToddThanks Todd for answering my question so adeptly. What you said makes a lot of sense. I think that my next move should be to do some serious research in this area. The other thought I had this week was that perhaps noradrenergics can compensate for some of the problems of low dopamine. OR, maybe the naturally increased NE can increase DA in a way that doesn't elicit too much overresponse from the autoreceptors. Sounds crazy I know but the reason I'm suggesting this is because of my experience this week. I was very busy working. The adrenaline was flowing and I felt good - more energized, motivated and happy (without feeling overly stressed-out) than I have in a long time. Does this make any sense at all to you? Any thoughts would be appreciated.
Kara
Posted by zeugma on October 16, 2004, at 16:55:04
In reply to Re: Downregulating dopamine autoreceptors » King Vultan, posted by karaS on October 16, 2004, at 14:52:32
hi kara and todd,
all of our thoughts have been moving along similar lines. i am convinced, given the nature of my response to strattera and provigil (I believe provigil operates at least partially through noradrenergic mechanisms) and my much less specific and strong response to Ritalin, that my noradrenergic system is at least partially functional, while my dopaminergic system is in dire shape. i tracked down this article about the involvement of alpha-1-b receptors (previously identified as crucial to Provigil's mechanism of action) as mediating the interplay between the NE and DA systems. This search was inspired by the fact that I'm probably going to try dexedrine next, and i know that amphetamines act more potently to release/inhibit reuptake of NE than DA.
It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking 1b-adrenergic receptors [1b-adrenergic receptor knock-outs (1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg D-amphetamine in 1bAR-KO mice [84 and 74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of D-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of 1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in 1bAR-KO than in WT littermates (28%; p < 0.001).
In rats however, prazosin, an 1-adrenergic antagonist, decreases D-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local D-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release.
Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of 1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that 1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-1-adrenergic properties.
http://www.jneurosci.org/cgi/content/full/22/21/9150
am i on the right track here?
-z
Posted by karaS on October 16, 2004, at 20:29:15
In reply to Re: Downregulating dopamine autoreceptors, posted by zeugma on October 16, 2004, at 16:55:04
> hi kara and todd,
>
> all of our thoughts have been moving along similar lines. i am convinced, given the nature of my response to strattera and provigil (I believe provigil operates at least partially through noradrenergic mechanisms) and my much less specific and strong response to Ritalin, that my noradrenergic system is at least partially functional, while my dopaminergic system is in dire shape. i tracked down this article about the involvement of alpha-1-b receptors (previously identified as crucial to Provigil's mechanism of action) as mediating the interplay between the NE and DA systems. This search was inspired by the fact that I'm probably going to try dexedrine next, and i know that amphetamines act more potently to release/inhibit reuptake of NE than DA.
If stimulants more potently release/inhibit reuptake of NE, then why is it assumed that those who react paradoxically to stimulants have hypersensitive DA (rather than NE) receptors? (Also, if this is the case, then amphetamines might not put me to sleep like Ritalin did?)
> It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking 1b-adrenergic receptors [1b-adrenergic receptor knock-outs (1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg D-amphetamine in 1bAR-KO mice [84 and 74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of D-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of 1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in 1bAR-KO than in WT littermates (28%; p < 0.001).
>
> In rats however, prazosin, an 1-adrenergic antagonist, decreases D-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local D-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release.
By “trans-synaptic mechanism”, you’re referring to the work of the 1-b adrenergic receptors, right? So you’re saying here that hypersensitive DA receptors might not be our problem (or might only be part of the problem) – and that the DA itself could instead be rendered “nonfunctional”?
> Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of 1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that 1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-1-adrenergic properties.
>
> http://www.jneurosci.org/cgi/content/full/22/21/9150
>
> am i on the right track here?
It's certainly food for thought. Thanks for posting this. I'm happy if it opens new avenues of exploration. I just wish that we were further along in the process!
Kara
Posted by King Vultan on October 17, 2004, at 0:15:35
In reply to Re: Downregulating dopamine autoreceptors » zeugma, posted by karaS on October 16, 2004, at 20:29:15
I think it's worth noting that I take doxazosin, which is an alpha-1 adrenergic antagonist in the same class as prazosin. It sounds like it may be decreasing some of the locomotor effects of the Parnate I'm taking; although, these effects are likely much smaller than those of amphetamine, anyway, because Parnate is a much weaker stimulant. This is also assuming my brain is somewhat similar to a rat brain in this regard.
Todd
Posted by Larry Hoover on October 17, 2004, at 9:58:06
In reply to Re: Downregulating dopamine autoreceptors, posted by King Vultan on October 17, 2004, at 0:15:35
> I think it's worth noting that I take doxazosin, which is an alpha-1 adrenergic antagonist in the same class as prazosin. It sounds like it may be decreasing some of the locomotor effects of the Parnate I'm taking; although, these effects are likely much smaller than those of amphetamine, anyway, because Parnate is a much weaker stimulant. This is also assuming my brain is somewhat similar to a rat brain in this regard.
>
> ToddWell, the only way to know for sure is to sample your brain tissue, so I think we are left with having to make certain assumptions.
Lar
Posted by yznhymer on October 19, 2004, at 8:04:40
In reply to Re: Downregulating dopamine autoreceptors, posted by King Vultan on October 17, 2004, at 0:15:35
Hmm. How are you with running mazes? ;-)
Mark
Posted by karaS on October 19, 2004, at 14:25:56
In reply to Re: Downregulating dopamine autoreceptors » King Vultan, posted by yznhymer on October 19, 2004, at 8:04:40
> Hmm. How are you with running mazes? ;-)
>
> Mark
Good one!
Posted by iris2 on October 19, 2004, at 14:33:54
In reply to Re: Downregulating dopamine autoreceptors, posted by King Vultan on October 17, 2004, at 0:15:35
What do you take the doxazosin for?
irene
Posted by King Vultan on October 20, 2004, at 22:25:08
In reply to Re: Downregulating dopamine autoreceptors » King Vultan, posted by iris2 on October 19, 2004, at 14:33:54
> What do you take the doxazosin for?
>
> irene
I have hypersensitive alpha-1 receptors in the prostate, causing constriction, and some minor urination difficulties. I didn't quite understand the nature of the problem or that anything could be done about it until I happened to take nortriptyline, and urination improved. The only reasonable explanation was nortriptyline's alpha-1 blockade. Then when I was on the extremely anticholinergic protriptyline, I had such severe urination difficulties, I asked to start taking some kind of alpha-1 blocker, which I am still taking umpteen drugs later. I could probably do without it, but it does slightly increase the quality of my life.Todd
Posted by Chairman_MAO on November 4, 2004, at 4:10:07
In reply to Re: Downregulating dopamine autoreceptors, posted by King Vultan on October 17, 2004, at 0:15:35
For what any anecdote is worth:
I used to take trazodone to sleep on Parnate. I absolutely hated it, primarily because of its adrenergic antagonism. I found it negated a good part of the motivational and anti-ADD effects of the Parnate that are essential for me.
At any rate, once I got over 150mg/day, the insomnia paradoxically disappeared, and I sleep like a baby. Jay Amsterdam's study of tranylcypromine in treatment-resistant depression is right on the money. At 200mg/day, I find Parnate profoundly calming, not activating. The insomnia is gone--although I can choose to stay up, as I did tonight, but that's a sleep hygene issue of mine that should not be band-aided with drugs--as is any agitation. The improvement in depression compared to, let's say, when I was taking 80mg/day is minimal, but the improvement in social phobia and self-esteem is INCREDIBLE and worlds beyond 80mg/day. Also, the hypersexuality of the lower (10-30mg/day) doses and the occasional anaorgasmia of 80mg/day seem averaged together to create a healthy, moderate sex drive with AMAZING orgasms and erotic sensorium.
I am convinced that the reason everyone thinks Nardil is better than Parnate for social phobia is that the doses of Parnate used are woefully inadequate. Honestly, I could not conceive of anyone needing any adjunctive medication for social phobia at 200mg/day, but if they did, I'm sure a pinch of clonazepam, beta-phenyl-GABA/baclofen, Neurontin, or your MAOI-friendly treatment of choice would fill in any gaps. I personally find that picamilon works wonders with it, although if there were a safe GABA-T inhibitor on the market, I'd definitely try that to push things more toward the Nardil end of things.
Maybe I should try a high quality valerian extract; anyone know of anything else besides Depakote, gama-vinyl-gaba, and the hydrazine MAOIs that inhibits GABA-T?
Best to all,
--cm
Posted by iris2 on November 4, 2004, at 11:57:10
In reply to Re: a1 antagonism + tranylcypromine, posted by Chairman_MAO on November 4, 2004, at 4:10:07
I am curiuos. Did you have many side effects from Parnate at the lower dosages of say 60-80mg? From how I read this you had insomnia? I was anxious had insomnia, hypotention like mad. It made it impossible for me to increase the dosage a high as you have gone. I ask because for several years Parnate helped me so much, better than any other nmedication I can take. It pooped out and I am wondering if after about six or seven years off of it if I tried to take it at a highter dose if it wouod help me again. I know at a lower dose it does not because I tried several times in the past few years.
What is your opinion?
Thanks,
irene
Posted by SLS on November 4, 2004, at 23:27:56
In reply to Re: a1 antagonism + tranylcypromine, posted by Chairman_MAO on November 4, 2004, at 4:10:07
Hi CM.
Do you dream at the higher dosages of Parnate?
Thanks.
- Scott
Posted by dreyfus on November 6, 2004, at 14:39:38
In reply to Re: a1 antagonism + tranylcypromine, posted by Chairman_MAO on November 4, 2004, at 4:10:07
> For what any anecdote is worth:
>
> I used to take trazodone to sleep on Parnate. I absolutely hated it, primarily because of its adrenergic antagonism. I found it negated a good part of the motivational and anti-ADD effects of the Parnate that are essential for me.
>
> At any rate, once I got over 150mg/day, the insomnia paradoxically disappeared, and I sleep like a baby. Jay Amsterdam's study of tranylcypromine in treatment-resistant depression is right on the money. At 200mg/day, I find Parnate profoundly calming, not activating. The insomnia is gone--although I can choose to stay up, as I did tonight, but that's a sleep hygene issue of mine that should not be band-aided with drugs--as is any agitation. The improvement in depression compared to, let's say, when I was taking 80mg/day is minimal, but the improvement in social phobia and self-esteem is INCREDIBLE and worlds beyond 80mg/day. Also, the hypersexuality of the lower (10-30mg/day) doses and the occasional anaorgasmia of 80mg/day seem averaged together to create a healthy, moderate sex drive with AMAZING orgasms and erotic sensorium.
>
> I am convinced that the reason everyone thinks Nardil is better than Parnate for social phobia is that the doses of Parnate used are woefully inadequate. Honestly, I could not conceive of anyone needing any adjunctive medication for social phobia at 200mg/day, but if they did, I'm sure a pinch of clonazepam, beta-phenyl-GABA/baclofen, Neurontin, or your MAOI-friendly treatment of choice would fill in any gaps. I personally find that picamilon works wonders with it, although if there were a safe GABA-T inhibitor on the market, I'd definitely try that to push things more toward the Nardil end of things.
>
> Maybe I should try a high quality valerian extract; anyone know of anything else besides Depakote, gama-vinyl-gaba, and the hydrazine MAOIs that inhibits GABA-T?
>
> Best to all,
>
> --cmYour posting interested me immensely. I have been on Parnate for most of the past 15 years. I began at 40mg daily and just recently increased from 70 to 80mg daily. I also take 150mg Trazodone at night. Additionally, for the past several years, I have been taking Ritalin to augment the Parnate.
Since I've gone to 80mg, I have also experienced anorgasia (wasn't that great at 70mg, but better). The thought of Amazing Orgasms is really exciting. I am a 56 year male and am not expecting the same type of orgasm that I had as a young man, but any improvement would be great. My libido is still pretty active.
Can you tell me how long it took you to get to 200mg Parnate? I would really like to give it a try. My p-doc generally lets me do what I want if I show him the research.
Dreyfus
Posted by Chairman_MAO on November 7, 2004, at 5:44:47
In reply to Re: a1 antagonism + tranylcypromine » Chairman_MAO, posted by SLS on November 4, 2004, at 23:27:56
Not every night, but at least several times per week I am aware that I dreamt, even if I cannot remember the content well.
Posted by Iansf on November 7, 2004, at 12:51:12
In reply to Re: a1 antagonism + tranylcypromine » SLS, posted by Chairman_MAO on November 7, 2004, at 5:44:47
Does increasing Parnate to 200mg also increase the chance of hypertensive crisis, or is the amount irrelevant once you pass a certain threshold?
Posted by Chairman_MAO on November 7, 2004, at 18:12:57
In reply to Re: a1 antagonism + tranylcypromine » Chairman_MAO, posted by iris2 on November 4, 2004, at 11:57:10
When the dose of Parnate is increased to approximately 120mg/day and beyond, the amphetamine-like metabolites counteract the hypotension, and it actually disappears, along with the insomnia, any agitation, anorgasmia, etc.
Posted by Chairman_MAO on November 7, 2004, at 18:18:04
In reply to Re: a1 antagonism + tranylcypromine, posted by Iansf on November 7, 2004, at 12:51:12
The degree of MAO inhibition is relevant, but past a certain dose it is probably irrelevant.
Posted by SLS on November 8, 2004, at 6:52:58
In reply to Re: a1 antagonism + tranylcypromine » Iansf, posted by Chairman_MAO on November 7, 2004, at 18:18:04
> The degree of MAO inhibition is relevant, but past a certain dose it is probably irrelevant.
I read an abstract years ago that postulated high-dosage Parnate resulted in the downregulation of 5-HT2 receptors. Low-dosage did not.
- Scott
Posted by Iansf on November 8, 2004, at 10:50:17
In reply to Re: a1 antagonism + tranylcypromine, posted by SLS on November 8, 2004, at 6:52:58
> > The degree of MAO inhibition is relevant, but past a certain dose it is probably irrelevant.
>
> I read an abstract years ago that postulated high-dosage Parnate resulted in the downregulation of 5-HT2 receptors. Low-dosage did not.
>
>
> - ScottWhat is the significance of that?
John Mc
Posted by SLS on November 8, 2004, at 23:28:19
In reply to Re: a1 antagonism + tranylcypromine » SLS, posted by Iansf on November 8, 2004, at 10:50:17
> > > The degree of MAO inhibition is relevant, but past a certain dose it is probably irrelevant.
> >
> > I read an abstract years ago that postulated high-dosage Parnate resulted in the downregulation of 5-HT2 receptors. Low-dosage did not.
> >
> >
> > - Scott
>
> What is the significance of that?
>
> John Mc
I would have to research the matter further to better understand it all, but it is known that several antidepressants (nefazodone, mirtazapine) and the atypical neuroleptics (which have antidepressant properties) block 5-HT2a receptors. 5-HT2 blockade or the downregulation of these receptors in the absence of reuptake inhibition might produce similar results. I don't know.
- Scott
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