Psycho-Babble Medication Thread 400754

Shown: posts 1 to 25 of 37. This is the beginning of the thread.

 

Parnate Discontinuation

Posted by ron1953 on October 9, 2004, at 14:25:53

I'm stopping the Parnate mainly because of extreme lethargy. My Pdoc says to step down by 10mg every 4 days (I'm at 40mg/day). I'd prefer to just stop cold turkey. I've seen recommendations about stopping Parnate 7-10 days before surgery, which obviously means cold turkey. Is my Pdoc being overly cautious? I've stopped many other meds cold turkey without problems. Any knowledge or experience shared will be appreciated.

Ron

 

Re: Parnate Discontinuation

Posted by Piquet on October 9, 2004, at 19:27:17

In reply to Parnate Discontinuation, posted by ron1953 on October 9, 2004, at 14:25:53

> I'm stopping the Parnate mainly because of extreme lethargy. My Pdoc says to step down by 10mg every 4 days (I'm at 40mg/day). I'd prefer to just stop cold turkey. I've seen recommendations about stopping Parnate 7-10 days before surgery, which obviously means cold turkey. Is my Pdoc being overly cautious? I've stopped many other meds cold turkey without problems. Any knowledge or experience shared will be appreciated.
>
> Ron

Hi Ron, Piquet here. I'm sorry that Parnate didn't work out for you -- it must be pretty disappointing. I once stopped Nardil (45 mg)cold turkey and got twitching and nervousness for a week or so. My guess is that doing the same with Parnate will be unpleasant but not life-threatening. Hopefully, others on the board will have more specific feedback. Have you decided what you'll try next? Whatever you do, I wish you all the best.

Piquet.


 

Re: Parnate Discontinuation » ron1953

Posted by karaS on October 9, 2004, at 20:36:35

In reply to Parnate Discontinuation, posted by ron1953 on October 9, 2004, at 14:25:53

I haven't tried it yet so I can't give you any advice on discontinuation. I just wanted to say that I'm sorry to hear that you're discontinuing it. I thought you posted earlier that it was working for you...

K

 

Re: Parnate Discontinuation

Posted by EERRIICC on October 10, 2004, at 2:56:06

In reply to Re: Parnate Discontinuation » ron1953, posted by karaS on October 9, 2004, at 20:36:35

I experienced very negative effects from stopping Parnate cold turkey; severe agitation and intense depression. I had to go back on it and taper down. I suggest you don't do it. I tapered down at 10mg per day from a 100mg dose and this was still very uncomfortable. Sometimes tapering off a medication at a "good" rate actually makes you feel better as it's going on. Ask Scott (screen name SLS) for his opinion.
Good luck!

 

Re: Parnate Discontinuation » ron1953

Posted by King Vultan on October 10, 2004, at 10:07:52

In reply to Parnate Discontinuation, posted by ron1953 on October 9, 2004, at 14:25:53

If it were Nardil, I think it's more important to not drop it cold turkey, but the advice to taper is probably still good. I tapered Nardil from 7 pills/day to 0 at 1 pill every three days and found this barely tolerable. However, Parnate is not as likely to hit with you with REM rebound as Nardil, which I found particularly nasty. I would still suggest not dropping the Parnate any faster than 1 pill every 3 days unless this lethargy is absolutely unbearable. Sorry it didn't work out for you. Parnate is turning out to be very neutral for me and relatively tolerable. Perhaps selegiline might be a better choice for you? I believe most people do find it more activating than Parnate, in some cases, ridiculously so.

Todd

 

Re: Parnate Experience » King Vultan

Posted by karaS on October 10, 2004, at 14:57:45

In reply to Re: Parnate Discontinuation » ron1953, posted by King Vultan on October 10, 2004, at 10:07:52

> If it were Nardil, I think it's more important to not drop it cold turkey, but the advice to taper is probably still good. I tapered Nardil from 7 pills/day to 0 at 1 pill every three days and found this barely tolerable. However, Parnate is not as likely to hit with you with REM rebound as Nardil, which I found particularly nasty. I would still suggest not dropping the Parnate any faster than 1 pill every 3 days unless this lethargy is absolutely unbearable. Sorry it didn't work out for you. Parnate is turning out to be very neutral for me and relatively tolerable. Perhaps selegiline might be a better choice for you? I believe most people do find it more activating than Parnate, in some cases, ridiculously so.
>
> Todd


Todd,
Do you mean that Parnate is neutral for you in terms of fatigue/energy and side effects? It's still working out well for you in terms of AD action, isn't it? Are you able to exercise on it? Does it help you with motivation and concentration?

I don't mean to drill you but since you may have the same issue that I do with regard to hypersensitive dopamine autoreceptors, I'm very interested in what works for you. Did you have good responses to any other ADs in the past? Do you also have paradoxical responses to stimulants/dopaminergics?

I'm starting Cymbalta soon. (I've been putting it off for a couple of reasons.) If that doesn't work out for me, then I'll probably try Marplan or Parnate - so any info you can give me would be appreciated.

Thanks,
Kara

 

Re: Parnate Experience » karaS

Posted by King Vultan on October 10, 2004, at 19:36:46

In reply to Re: Parnate Experience » King Vultan, posted by karaS on October 10, 2004, at 14:57:45


>
>
> Todd,
> Do you mean that Parnate is neutral for you in terms of fatigue/energy and side effects? It's still working out well for you in terms of AD action, isn't it? Are you able to exercise on it? Does it help you with motivation and concentration?
>
> I don't mean to drill you but since you may have the same issue that I do with regard to hypersensitive dopamine autoreceptors, I'm very interested in what works for you. Did you have good responses to any other ADs in the past? Do you also have paradoxical responses to stimulants/dopaminergics?
>
> I'm starting Cymbalta soon. (I've been putting it off for a couple of reasons.) If that doesn't work out for me, then I'll probably try Marplan or Parnate - so any info you can give me would be appreciated.
>
> Thanks,
> Kara
>

It's neutral for me as far as stimulation vs. sedation. However, since I tend to be rather anergic and lethargic in an unmedicated state, I suppose it has been activating in that respect. It is definitely helping both my concentration and motivation and seems pretty effective as an antidepressant. I've been at 50 mg/day for a week now, and on this dosage increase, I haven't suffered the significant bouts of depression I experienced going from 20 to 30 and 30 to 40, well at least not yet, anyway. Perhaps my hypersensitive autoreceptors were mostly down regulated by the two previous dosage increases. I am able to exercise much easier on it than I was on Nardil, and it seems to have no negative impacts in that area. I took my heart monitor out with me while running 6+ miles today, and it was mostly reading between 140-160 while running at a good but not overly strenuous pace that probably would not have been possible on the Nardil.

The drugs I've tried that I've suffered excessive sedation on were Provigil, Strattera, and nortriptyline. Nortriptyline also induced some amount of depression at first, and trazodone caused intolerable depression when I was on Nardil. I believe that in every case, this can be related to the issue of hypersensitive dopamine autoreceptors, as I believe all these drugs do have a secondary dopaminergic effect (nortriptyline and trazodone from blockading 5-HT2A receptors, the same as atypical antipsychotics do). I was thinking of perhaps trying the trazodone again at some point and see if it doesn't work better on Parnate. I expect it probably will, and if so, this would also tend to confirm the hypothesis that my dopamine autoreceptors have been effectively downregulated.

As for the other drugs I've had positive antidepressant responses to without unusual sedation, these would include Prozac, Effexor, Zoloft, Wellbutrin, desipramine, protriptyline, and Nardil.

Todd

 

Re: Parnate Experience » King Vultan

Posted by karaS on October 10, 2004, at 23:11:26

In reply to Re: Parnate Experience » karaS, posted by King Vultan on October 10, 2004, at 19:36:46

Thanks, Todd

I think I'm more confused than ever. I guess I can't completely draw any conclusions from your experiences since we have significant differences in medication effects and successes.

I have taken selegiline, Ritalin, Rhodiola and Perika brand of SJW. All are supposed to be very stimulating and have significant dopaminergic activity. They all put me to sleep. I am convinced at this point that I could take methamphetamine and fall asleep as well. However, when I took nortriptyline, I was so energized and activated. When I took Provigil, it didn't put me to sleep at all. It had very little effect in that respect. All of this makes me wonder if your problem isn't more to do with NE? I suppose if you tried selegiline or Ritalin or another stimulant, you'd know for certain.

I'm also confused as to why you think it's possible to down regulate the DA autoreceptors when Dr. Jay Goldstein and my pdoc both told me that there are no medications as of yet to treat hypersensitive dopamine autoreceptors. There is supposedly at least one that's in testing now however. I know you said previously that you thought certain ADs could act like the SSRIs and downregulate dopamine in the same way that those meds do with respect to serotonin. But then why do the 2 doctors say that there are no medications yet to treat this condition?

I hope it doesn't sound like I'm jumping all over you here, I am just trying to understand...

At any rate, I'm really glad that you're having so much success with Parnate. Positive AD effect, better motivation and concentration and you can exercise too! What more could you ask for? Sounds like heaven to me.

K

> It's neutral for me as far as stimulation vs. sedation. However, since I tend to be rather anergic and lethargic in an unmedicated state, I suppose it has been activating in that respect. It is definitely helping both my concentration and motivation and seems pretty effective as an antidepressant. I've been at 50 mg/day for a week now, and on this dosage increase, I haven't suffered the significant bouts of depression I experienced going from 20 to 30 and 30 to 40, well at least not yet, anyway. Perhaps my hypersensitive autoreceptors were mostly down regulated by the two previous dosage increases. I am able to exercise much easier on it than I was on Nardil, and it seems to have no negative impacts in that area. I took my heart monitor out with me while running 6+ miles today, and it was mostly reading between 140-160 while running at a good but not overly strenuous pace that probably would not have been possible on the Nardil.
>
> The drugs I've tried that I've suffered excessive sedation on were Provigil, Strattera, and nortriptyline. Nortriptyline also induced some amount of depression at first, and trazodone caused intolerable depression when I was on Nardil. I believe that in every case, this can be related to the issue of hypersensitive dopamine autoreceptors, as I believe all these drugs do have a secondary dopaminergic effect (nortriptyline and trazodone from blockading 5-HT2A receptors, the same as atypical antipsychotics do). I was thinking of perhaps trying the trazodone again at some point and see if it doesn't work better on Parnate. I expect it probably will, and if so, this would also tend to confirm the hypothesis that my dopamine autoreceptors have been effectively downregulated.
>
> As for the other drugs I've had positive antidepressant responses to without unusual sedation, these would include Prozac, Effexor, Zoloft, Wellbutrin, desipramine, protriptyline, and Nardil.
>
> Todd

 

Exercise problems with Nardil or Parnate?

Posted by gardenergirl on October 11, 2004, at 0:02:35

In reply to Re: Parnate Experience » King Vultan, posted by karaS on October 10, 2004, at 23:11:26

Sorry to go off a bit on a tangent, but Todd mentioned being able to exercise better on Parnate than on Nardil. May I ask for more details, please? Is it motivation or physical effort? I am on Nardil, and I want to try to combat the weight gain (40-50 pounds in the last year). I have found I get short of breath and fatigued much more quickly when exercising, plus I sweat like crazy. I attributed this to the weight gain, but is there something about Nardil that makes it so much harder?

Thanks in advance,
gg

 

Oops, just saw maddog's thread on same topic (nm)

Posted by gardenergirl on October 11, 2004, at 0:15:36

In reply to Exercise problems with Nardil or Parnate?, posted by gardenergirl on October 11, 2004, at 0:02:35

 

Re: Exercise problems with Nardil or Parnate? » gardenergirl

Posted by King Vultan on October 11, 2004, at 8:09:43

In reply to Exercise problems with Nardil or Parnate?, posted by gardenergirl on October 11, 2004, at 0:02:35

> Sorry to go off a bit on a tangent, but Todd mentioned being able to exercise better on Parnate than on Nardil. May I ask for more details, please? Is it motivation or physical effort? I am on Nardil, and I want to try to combat the weight gain (40-50 pounds in the last year). I have found I get short of breath and fatigued much more quickly when exercising, plus I sweat like crazy. I attributed this to the weight gain, but is there something about Nardil that makes it so much harder?
>
> Thanks in advance,
> gg

I've been exercising for so long there's no problem with motivation; the problem I ran into with Nardil was that I did not seem to be able to run as fast putting forth the same amount of physical effort, plus it caused these weird weakness/dizziness spells when I would first start running. I actually increased my weekly mileage while on Nardil because I was putting on weight but was barely able to hold my own against the weight gain. Parnate seems much better as far as both exercising and weight gain.

Todd

 

Re: Parnate Experience » karaS

Posted by King Vultan on October 11, 2004, at 9:36:12

In reply to Re: Parnate Experience » King Vultan, posted by karaS on October 10, 2004, at 23:11:26

> Thanks, Todd
>
> I think I'm more confused than ever. I guess I can't completely draw any conclusions from your experiences since we have significant differences in medication effects and successes.
>
> I have taken selegiline, Ritalin, Rhodiola and Perika brand of SJW. All are supposed to be very stimulating and have significant dopaminergic activity. They all put me to sleep. I am convinced at this point that I could take methamphetamine and fall asleep as well. However, when I took nortriptyline, I was so energized and activated. When I took Provigil, it didn't put me to sleep at all. It had very little effect in that respect. All of this makes me wonder if your problem isn't more to do with NE? I suppose if you tried selegiline or Ritalin or another stimulant, you'd know for certain.
>
> I'm also confused as to why you think it's possible to down regulate the DA autoreceptors when Dr. Jay Goldstein and my pdoc both told me that there are no medications as of yet to treat hypersensitive dopamine autoreceptors. There is supposedly at least one that's in testing now however. I know you said previously that you thought certain ADs could act like the SSRIs and downregulate dopamine in the same way that those meds do with respect to serotonin. But then why do the 2 doctors say that there are no medications yet to treat this condition?
>
> I hope it doesn't sound like I'm jumping all over you here, I am just trying to understand...
>
> At any rate, I'm really glad that you're having so much success with Parnate. Positive AD effect, better motivation and concentration and you can exercise too! What more could you ask for? Sounds like heaven to me.
>
> K
>

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.

Todd

 

Re: Exercise problems with Nardil or Parnate? » King Vultan

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.
>
> 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

 

Re: Exercise problems with Nardil or Parnate?

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

 

Re: Exercise problems with Nardil or Parnate? » gardenergirl

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

 

Re: Exercise problems...and maddog » King Vultan

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

 

Re: Exercise problems with Nardil or Parnate? » gardenergirl

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

 

Re: Downregulating dopamine autoreceptors » King Vultan

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.
>
> Todd

Thanks 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

 

Re: Downregulating dopamine autoreceptors

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

 

Re: Downregulating dopamine autoreceptors » zeugma

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

 

Re: Downregulating dopamine autoreceptors

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

 

Re: Downregulating dopamine autoreceptors » King Vultan

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.
>
> Todd

Well, 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

 

Re: Downregulating dopamine autoreceptors » King Vultan

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

 

Re: Downregulating dopamine autoreceptors » yznhymer

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!

 

Re: Downregulating dopamine autoreceptors » King Vultan

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


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