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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 becksA on July 10, 2004, at 21:00:45
Just wondering how Pamelor works chemically in the brain...Thanks
Posted by King Vultan on July 11, 2004, at 0:50:02
In reply to Pamelor - How does it work, posted by becksA on July 10, 2004, at 21:00:45
> Just wondering how Pamelor works chemically in the brain...Thanks
It's a selective norepinephrine reuptake inhibitor, meaning it selectively targets the neurotransmitter norepinephrine by a factor of at least 10x more than it does serotonin. SSRIs such as Lexapro and Prozac OTOH target serotonin.
Pamelor (nortriptyline) also blockades histamine receptors (meaning it is an antihistamine), which is responsible for some of the sedative and anti-anxiety effects of the drug. It also has a couple of other blockades of note--it blockades serotonin-2 receptors, which has a number of effects, including adding to the sedative and anti-anxiety effects of the histamine blockade. It also blockades alpha-1 adrenergic receptors, which is responsible for the lower blood pressure and dizziness that some experience on the drug, as well as further adding to sedation.
So the drug has a totally different pharmacologic profile from that of the common SSRIs, which have none of these characteristics. In general, Pamelor is sedating, calming, and works on a different neurotransmitter than do the SSRIs, albeit, one that is equally or more important. It can be a good choice for people who have a lack of response to SSRIs or tolerate SSRI side effects poorly.
Todd
Posted by becksA on July 11, 2004, at 9:46:28
In reply to Re: Pamelor - How does it work, posted by King Vultan on July 11, 2004, at 0:50:02
thanks a lot.
Posted by KaraS on July 15, 2004, at 1:33:28
In reply to Re: Pamelor - How does it work, posted by King Vultan on July 11, 2004, at 0:50:02
> > Just wondering how Pamelor works chemically in the brain...Thanks
>
> It's a selective norepinephrine reuptake inhibitor, meaning it selectively targets the neurotransmitter norepinephrine by a factor of at least 10x more than it does serotonin. SSRIs such as Lexapro and Prozac OTOH target serotonin.
>
> Pamelor (nortriptyline) also blockades histamine receptors (meaning it is an antihistamine), which is responsible for some of the sedative and anti-anxiety effects of the drug. It also has a couple of other blockades of note--it blockades serotonin-2 receptors, which has a number of effects, including adding to the sedative and anti-anxiety effects of the histamine blockade. It also blockades alpha-1 adrenergic receptors, which is responsible for the lower blood pressure and dizziness that some experience on the drug, as well as further adding to sedation.
>
> So the drug has a totally different pharmacologic profile from that of the common SSRIs, which have none of these characteristics. In general, Pamelor is sedating, calming, and works on a different neurotransmitter than do the SSRIs, albeit, one that is equally or more important. It can be a good choice for people who have a lack of response to SSRIs or tolerate SSRI side effects poorly.
>
> ToddTodd,
Why does it produce tachycardia in some people (like me) and not in others? (That's probably not a fair question since many of us can be fairly idiosyncratic in our reactions.) Also, I'm assuming that the tachycardia is in response to NE activity and I'm wondering if I will react to all meds that act on NE that same way (even though I desperately need to stimulate NE activity).
Kara
Posted by King Vultan on July 15, 2004, at 8:17:32
In reply to Re: Pamelor - How does it work, posted by KaraS on July 15, 2004, at 1:33:28
>
> Todd,
> Why does it produce tachycardia in some people (like me) and not in others? (That's probably not a fair question since many of us can be fairly idiosyncratic in our reactions.) Also, I'm assuming that the tachycardia is in response to NE activity and I'm wondering if I will react to all meds that act on NE that same way (even though I desperately need to stimulate NE activity).
> Kara
Tachycardia is also an anticholinergic effect, which may also be playing a role here. Nortriptyline's ACh effects are regarded as being rather mild, but it is derived from amitriptyline, the most anticholinergic of all antidepressants, and some people are perhaps reacting to this effect. I honestly can't remember if I suffered much tachycardia on nortriptyline; I think my heart rate was elevated, but perhaps only into the 80's. On desipramine, which is a more powerful NE reuptake inhibitor and has very low ACh effects (for a tricyclic), I experienced definite tachycardia. On protripyline, which is about as powerful an NE reuptake inhibitor as desipramine but is drastically more anticholinergic, I suffered even worse tachycardia.In answer to your question, though, people obviously can have different reactions to the same med, probably due to differences in receptor densities or some other darned thing. I seem to be relatively sensitive to the tachycardia effect myself but viewed an occasional reading at rest of between 100-110 without a great deal of alarm when I was on these drugs. Seeing it occasionally go over 110 frankly made me a bit nervous, but most of the time it seemed to be in the 90's, even on protriptyline, and considering my cardiovascular health seems to be very good to begin with, I came to regard these readings without a great deal of concern.
Todd
Posted by SLS on July 15, 2004, at 8:55:48
In reply to Re: Pamelor - How does it work, posted by KaraS on July 15, 2004, at 1:33:28
> Also, I'm assuming that the tachycardia is in response to NE activity and I'm wondering if I will react to all meds that act on NE that same way (even though I desperately need to stimulate NE activity).
It is a combination of actions leading to an autonomic imbalance:
1. pro-NE increased sympathetic
2. anti-ACh decreased parasympathetic
- Scott
Posted by KaraS on July 15, 2004, at 16:45:56
In reply to Re: Pamelor - How does it work » KaraS, posted by King Vultan on July 15, 2004, at 8:17:32
>
> >
> > Todd,
> > Why does it produce tachycardia in some people (like me) and not in others? (That's probably not a fair question since many of us can be fairly idiosyncratic in our reactions.) Also, I'm assuming that the tachycardia is in response to NE activity and I'm wondering if I will react to all meds that act on NE that same way (even though I desperately need to stimulate NE activity).
> > Kara
>
>
> Tachycardia is also an anticholinergic effect, which may also be playing a role here. Nortriptyline's ACh effects are regarded as being rather mild, but it is derived from amitriptyline, the most anticholinergic of all antidepressants, and some people are perhaps reacting to this effect. I honestly can't remember if I suffered much tachycardia on nortriptyline; I think my heart rate was elevated, but perhaps only into the 80's. On desipramine, which is a more powerful NE reuptake inhibitor and has very low ACh effects (for a tricyclic), I experienced definite tachycardia. On protripyline, which is about as powerful an NE reuptake inhibitor as desipramine but is drastically more anticholinergic, I suffered even worse tachycardia.
>
> In answer to your question, though, people obviously can have different reactions to the same med, probably due to differences in receptor densities or some other darned thing. I seem to be relatively sensitive to the tachycardia effect myself but viewed an occasional reading at rest of between 100-110 without a great deal of alarm when I was on these drugs. Seeing it occasionally go over 110 frankly made me a bit nervous, but most of the time it seemed to be in the 90's, even on protriptyline, and considering my cardiovascular health seems to be very good to begin with, I came to regard these readings without a great deal of concern.
>
> Todd
Todd,Thank you for all of that info. One thing I wanted to clarify, you said that you weren't alarmed by "occassional" readings of 100-110 bmp. Does that also pertain if your constant resting state were in that range?
In general, from reading several of your posts, I want to say that you have a clear and concise way of writing that makes technical information very understandable.
Thanks again,
Kara
Posted by KaraS on July 15, 2004, at 16:51:52
In reply to Re: Pamelor - How does it work, posted by SLS on July 15, 2004, at 8:55:48
> > Also, I'm assuming that the tachycardia is in response to NE activity and I'm wondering if I will react to all meds that act on NE that same way (even though I desperately need to stimulate NE activity).
>
> It is a combination of actions leading to an autonomic imbalance:
>
> 1. pro-NE increased sympathetic
>
> 2. anti-ACh decreased parasympathetic
>
>
> - ScottThanks, Scott. Just wish I reacted less to it but I've definitely put nortriptyline back on the list to try (at your suggestion).
- K
Posted by King Vultan on July 16, 2004, at 7:52:58
In reply to Re: Pamelor - How does it work, posted by KaraS on July 15, 2004, at 16:45:56
>
>
> Todd,
>
> Thank you for all of that info. One thing I wanted to clarify, you said that you weren't alarmed by "occassional" readings of 100-110 bmp. Does that also pertain if your constant resting state were in that range?
>
> In general, from reading several of your posts, I want to say that you have a clear and concise way of writing that makes technical information very understandable.
>
> Thanks again,
> Kara
Taking all readings into account, my resting rates on desipramine and protriptyline both averaged in the 90's, which was below the 100 bpm level indicated by my pdoc as the threshold of concern. I tend to defer to the judgement of the doctor I'm dealing with, so I certainly would have alerted him if the rate were averaging over 100 bpm, plus probably doing some research on how tachycardia is looked at and defined by various authorities to discuss that with him also. Other doctors may have a different threshold of concern, perhaps 110 bpm, for instance. I am not a real expert on the subject, however.Todd
Posted by ravenstorm on July 16, 2004, at 16:54:21
In reply to Re: Pamelor - How does it work » KaraS, posted by King Vultan on July 16, 2004, at 7:52:58
I tried Nortript. back in December at only 10mg for four days and it felt like my heart was beating a mile a minute right after I took the drug. That, combined with my husband bringing home a bunch of books that claimed that all antidepressants damage your brain/make you worse in the long wrong, made me stop the trial. (So helpful of him, considering I was suicidal after the apocalyptic paxil withdrawal.) I then started all the naturopathic stuff which did nothing but ruin my stomach.
I am regretting that I didn't give it more of a try.
I am currently on remeron 15mg which has helped the anxiety but I don't feel anywhere near as good as I did on paxil (for the first two years anyway). The longer I am on the remeron the more exhausted I feel (It has been three or four months). My pdoc has rx'd wellbutrin but I haven't started it yet. I don't want to be on a cocktail and part of me was hoping to just hang in on the 15mg remeron until finding out one way or the other (hopefully some news by August)wether or not the selegeline patch is going to gain final approval. But I don't know how much longer I can stay in this limbo. I am so freakin' tired.
I wish I knew if I'd be able to handle the nortrip or not. Will nortrip be way too sedating if remeron is? (I actually had lots of energy the first three weeks--must have been hypomanic) Now I'll probably have to go through withdrawal from remeron to switch.
God I hate this. In September it will be a year of this and still no "final" (for at least a couple of years?) drug. Considering a change would be sooo much easier if I didn't get so damned sick going on and off these things.
Sorry to complain, Scott. I don't know how you keep going through it!
Posted by ravenstorm on July 17, 2004, at 15:24:45
In reply to Re: Pamelor - How does it work, posted by ravenstorm on July 16, 2004, at 16:54:21
Just reread my post and can't believe how stupid I am on this remeron!! I hate it. I wrote the "long wrong" instead of the long run. I can't believe the cognitive blunting of this drug. I wasn't like this on paxil. My memory is also totally shot. Sigh.
Does notrip. also cause cognitive blunting?
Posted by KaraS on July 17, 2004, at 20:47:33
In reply to Re: Pamelor - How does it work, posted by ravenstorm on July 17, 2004, at 15:24:45
> Just reread my post and can't believe how stupid I am on this remeron!! I hate it. I wrote the "long wrong" instead of the long run. I can't believe the cognitive blunting of this drug. I wasn't like this on paxil. My memory is also totally shot. Sigh.
>
> Does notrip. also cause cognitive blunting?I know of many who call the tricyclics "dumb drugs" because of their anticholinergic effects and because they're "dirty" in the sense that they don't cleanly or directly hone in on the problem (probably not a great way of explaining it but you get the gist). Desipramine is usually excluded from that categorizition because it is the least anticholinergic and quite stimulating.
On the otherhand, I've heard of many people who have a lot more clarity (as well as relief from depression) once they've taken nortriptyline. Some people tend to be sedated on it while others find it very stimulating. I think that the more sedating, more ACh drugs are the ones with the most cognitive blunting. I wonder if those who find nortriptyline stimulating, have less cognitive blunting from it. (SLS? Todd?)
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