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Pramipexole


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#31 StrangeAeons

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Posted 23 May 2009 - 09:53 PM

supposedly the RLS is waking me up during sleep, so I imagine that it might have an indirect antidepressant effect simply by improving sleep quality. As to dividing doses, I'm not convinced it makes any significant difference aside from maybe its activity fluctuating a bit over the course of the day. I'm really taking it for the long-term aspects, in the hope that it might offset the D2 receptor damage and other monoaminergic deficits that have likely been induced by iron deficiency. Is there any literature on dividing doses? None of that seems to be mentioned in the more readily accessible materials on this drug.

Other reasons: I also have elevated prolactin and a refractory depression characterized strongly by anhedonia and avolition.

I also have a familial diathesis to obsessive cognition, schizotypal traits, and anxiety. 3 out of 4 of my grandparents have psychiatric problems, 3 out of 5 of my blood aunts/uncles are on psych meds, and my father's had recurring major depressive episodes which respond partially to low doses of fluoxetine but I suspect he still has quite a bit of trouble...
I am so not reproducing within the incredibly limited gene pool that is Ashkenazic Jews.
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#32 hullcrush

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Posted 24 May 2009 - 07:35 PM

supposedly the RLS is waking me up during sleep, so I imagine that it might have an indirect antidepressant effect simply by improving sleep quality. As to dividing doses, I'm not convinced it makes any significant difference aside from maybe its activity fluctuating a bit over the course of the day. I'm really taking it for the long-term aspects, in the hope that it might offset the D2 receptor damage and other monoaminergic deficits that have likely been induced by iron deficiency. Is there any literature on dividing doses? None of that seems to be mentioned in the more readily accessible materials on this drug.

Other reasons: I also have elevated prolactin and a refractory depression characterized strongly by anhedonia and avolition.

I also have a familial diathesis to obsessive cognition, schizotypal traits, and anxiety. 3 out of 4 of my grandparents have psychiatric problems, 3 out of 5 of my blood aunts/uncles are on psych meds, and my father's had recurring major depressive episodes which respond partially to low doses of fluoxetine but I suspect he still has quite a bit of trouble...
I am so not reproducing within the incredibly limited gene pool that is Ashkenazic Jews.


JAP here, looking for love. Anyways, I've had a more positive experience with pramipexole after lowering the dosage to .0625 and taking it during night. Motivation is high, sex drive is nil, but that's OK because I hate sex ;) I think taking it within a week of selegiline really shut the testes down, due to the negative affects of LH and FSH release.

Could I suggest taking it with St. John's Wort?
In vitro unpublished research by a German PhD says that an explanation for SJW activity could be due to not only MAOI but dopamine hydroxylase inhibition.

I emailed them a bit back and his/her? full paper says that the antidepressant effect on hyperforin is probably due to mild serotonin and moderate dopamine release (in vivo), while norepinephrine is blocked. Virtually the same function as pramipexole. PEX doesn't interfere with any P450 concentrations, especially CYP3A4, St. John's Wort's inducer.

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#33 StrangeAeons

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Posted 24 May 2009 - 08:08 PM

lol@ the JAP comment.


what are you taking PEX for? That's an incredibly low dose, and it might just be stipulation here but at that dose you might only be hitting the autoreceptors (or perhaps serotonin receptors?) which would explain the dead sex drive.
Also, how SJW works is still wildly up in the air; it's difficult enough understanding psychotropic drugs with a relatively elucidated mechanism, but herbal extracts have a wide variety of psychoactive compounds; all of which may or may not interact with one another.
Bottom line, I'd prefer clinical evidence of something's effectiveness instead of a theoretical mechanism any day of the week, but I don't have that luxury here. I am considering augmenting it with an RIMA, which is something I've discussed in a rant thread on the free speech forum (they tend to bleed together).

#34 VespeneGas

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Posted 24 May 2009 - 08:14 PM

Funk recommends thrice daily dosing just because the half life is short, and several people on the M&M forums report crashy type symptoms when blood levels drop off. If you haven't already, it's really worth reading that thread, there's some pretty interesting analysis from Ex Dubio wrt mechanism etc, and some good anecdotal experiences.

I wish you the best of luck. Keep us posted!

#35 hullcrush

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Posted 24 May 2009 - 08:26 PM

lol@ the JAP comment.


what are you taking PEX for? That's an incredibly low dose, and it might just be stipulation here but at that dose you might only be hitting the autoreceptors (or perhaps serotonin receptors?) which would explain the dead sex drive.
Also, how SJW works is still wildly up in the air; it's difficult enough understanding psychotropic drugs with a relatively elucidated mechanism, but herbal extracts have a wide variety of psychoactive compounds; all of which may or may not interact with one another.
Bottom line, I'd prefer clinical evidence of something's effectiveness instead of a theoretical mechanism any day of the week, but I don't have that luxury here. I am considering augmenting it with an RIMA, which is something I've discussed in a rant thread on the free speech forum (they tend to bleed together).


I'm just in a testing period for PEX for toleration. I've titrated up to .375 and it was really bad fatigue. My only symptom is fatigue so... trying to ameloriate that.

My dopamine level is 0 units according to Labcorp, and norepinephrine is 2x reference. I think this adequately reflects my personality, even if there was a draw error or lab error or just bad timing. I ordered Meclobomide a few days back. Should take about 21 days or so. Thought it might be a prolactin tumor overriding dopamine but my level is perfect.

Hope your RIMA improves QOL because everyone's picking drugs that look awesome on paper.

#36 StrangeAeons

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Posted 24 May 2009 - 09:24 PM

I'm exceptionally wary of concluding anything from plasma catecholamine; these tests were not designed to be used in a psychiatric context. At the very least these labs should be taken from CSF if they're to mean anything wrt the CNS; but of course, orthomolecular docs aren't too keen on selling their patients a spinal tap.
I don't know how many times I have to say it, but looking at levels of any neurotransmitter isn't an effective correlate of personality, or vice versa. It's just not that simple.
Aside from that, these labs are designed to really test for pheochromocytoma, which is obviously rather extreme. As such, it's very common for dopamine to fall below detectable ranges; the test is designed to find high levels.
If you truly suspect prolactinoma, the lab you should look at is prolactin. If it's really high, you should have symptoms like impotence, gynecomastia, and lactation.

And thanks for the reminder VespeneGas; I looked at the M&M thread a while back but it would be good to review it. The tablets are only scored halfway, but I might try it out. As is I currently seem to break out in a sweat an hour or two after taking the stuff and feel somewhat nauseous, but it's transient and seems to have decreased with each subsequent dose.

#37 StrangeAeons

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Posted 26 May 2009 - 09:53 PM

I've looked over the M&M thread, very interesting stuff.

Pramipexole update:


(skip this paragraph if you want to get to the results)

I feel a lot of strange states normally, and with medication like this I'm looking for a game changer; something that enables me to radically alter my behavior for the better (less lethargic, less anxious, more assertive) and fundamentally changes my cognitive and emotional experience (less obsession, more confidence and optimism, hedonic tone, a sense of passion, more intense response to both pleasurable and intellectual stimuli), In that vein no psychotropic medication has yet induced these types of sensations; Provigil induced a modest increase in "busy-body" type behaviors, and also curbed appetite-- sometimes to the extent that I would suddenly realize I had gone up to 20 hours without eating anything. One day when I was on Wellbutrin and Zoloft (under whose auspices my academic career took a shit and died) I accidentally dosed twice, and felt a sudden optimism and happiness, and also noticed while in intro guitar class that my arpeggios were much more fluid. Motor command is among the litany of my deficits. These are about the only positive effects medications have ever had on me. Fortunately (if you look at it that way) all obligations in my life have come to a grinding halt for the next couple of weeks, and so I have this period of time completely free to cope with whatever adverse effects PPX might have. On the flip side of things, I really don't feel comfortable imposing any more obligations upon myself until I can achieve some measure of improvement.

With this in mind, I have been on pramipexole since last Thursday (this being my fifth day on it). I started with 0.5mg in the late afternoon, and would feel somnolent afterwords. This was usually resolved by a nap at some point, whose length it appears has gotten shorter as the regimen proceeds. I also initially developed a flop sweat and some nausea after the first two days of dosing, but this has lowered considerably. On Monday I was still awake at 4a.m. (my sleep cycle is horrendously erratic, unresponsive to melatonin) and felt some of the old night-panic that grips me from time to time. I decided I'd escalate the dose and took 0.5mg them and slept, then took 0.25mg in the late afternoon. I went to bed at 2a.m. last night and woke up at 4 noticing an odd vibratory sensation waking me up. It was highly pleasurable, but not sexual in nature. My perception was different, and I think it was because the autoreceptor agonism was wearing off and I was getting a little hint of rebound. I tried testing my motor command (via sequenced finger movements) while lying there in bed for a minute, and found that it wasn't at all improved. My perception was slightly altered, and I felt more confident, but the bulk of it wore off within a minute. Like I said, I go through a lot of odd states but rarely are they positive in nature.
I've committed myself now to a t.i.d dosing schedule, 0.25mg each day until the 8th day, at which point I'll double the night, then the afternoon, then the morning dose over the next three days until I've hit 0.5mg t.i.d. I'll give that another two weeks or so.

after that the treatment algorithm is as follows:

-no response to PPX: scale down dose and switch to RIMA's. Consider scaling back up once on RIMA's

-mild response: scale up dosage up to 5.0mg over the next ~6 weeks. The M&M thread cited a study on dose-dependent response as an antidepressant, but with a high dropout rate. Escalating slowly on a t.i.d. schedule should be beneficial. Augment with RIMA's when maximum dose has been reached.

-moderate response: same as above, but no augmentation necessary. More aggressive dose escalation, and titrate to optimum dose.

-strong response: maintain dosage, and get on with my life.

#38 VespeneGas

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Posted 28 May 2009 - 02:10 AM

Good luck, part of my hope for your success is pure self interest, as I've been mired in apathy, lethargy, anhedonia and lack of libido for, well, almost nine months now, and bupropion isn't helping, and I don't think amphetamine is a net positive in my life.

Please keep us updated. For reference, is there any thread where you've laid out your psychological condition in any completeness? I just remember from the "is it the dopamine?" thread that you were (inappropriately) treated with antipsychotics in your teens.

#39 hullcrush

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Posted 28 May 2009 - 06:49 PM

@strange: I don't expect plasma catecholamines to reflect neurotransmission whatsoever. my bp is 135/90, I was curious.

This is a scientific board, but it seems pramipexole has the same properties as SAM-e. I'm not sure of pramipexole's mechanism, but drugs are complex enough that it could be a methylation donor. At low doses, sam-e agonizes alpha-2, just like PEX. At higher doses, it increases dopaminergic transmission, reduces prolactin.

edit: it's =/= its

Edited by hullcrush, 28 May 2009 - 06:51 PM.


#40 bran319

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Posted 28 May 2009 - 08:15 PM

Do you have a reference for your SAM-e/Alpha-2 assertion? Thanks.

#41 hullcrush

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Posted 28 May 2009 - 10:16 PM

Do you have a reference for your SAM-e/Alpha-2 assertion? Thanks.


Solely a postulate based on access I had to this full article. I can't really think of another explanation. Vasodilation, angiotensin modification are the only other things I can think of. Maybe it accelerates the degradation of endogenous pressor agents....

#42 StrangeAeons

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Posted 29 May 2009 - 06:37 AM

I'm going to go ahead and say that there's no real mystery to the fact that PEX is a neurotransmitter ligand, chiefly active at dopamine receptors;
it's pretty well established. The analogy to SAMe seems a little silly; I don't see any need to implicate methyl donation in the whole affair.

As for checking catecholamines, I mention it because it's what the orthomolecular psychiatrist I went to see ordered. I don't see why in the world, though, you would think to check catecholamines for marginal essential hypertension; that's really chasing a zebra.

VG, there are a number of threads where I've progressively described my issues, and unfortunately I don't have any links off hand. There's a rantish thread in Free Speech entitled "I can't catch a fucking break!", and there's a thread in supplements entitled "Orthomolecular regimens" while I was still seeing one. Basically I've run the gamut of psychiatric diagnosis over the past 10 years (though I've had lifelong issues, my parents only really cared to intervene until I couldn't progress with school anymore). There's no real diagnosis for me, but I'd say chiefly anergic and agitated depression marked my anhedonia and avolition. Additionally anxiety, erratic sleep, obsessive cognition (no marked compulsions) and some schizotypal/narcissistic type thinking with regards to others. I have been referred to by a number of said professionals as fairly anomalous.

Edited by StrangeAeons, 29 May 2009 - 06:39 AM.


#43 StrangeAeons

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Posted 25 June 2009 - 07:16 AM

Okay, basically because the dose I want to take is much higher than the prescribed dose I've needed to order pramipexole online from alldaychemist (they were dramatically cheaper than any other source I've seen). In the meantime I'm only taking 0.5mg t.i.d. to avoid getting stuck without and going from a high dose to nothing like I managed to do a few weeks ago. I've been tracking the package and it's been in customs for 64 hours now.

I know it's a tangent, but how long should a package be in customs? Soon it will be 72 hours and that gets me very worried; if it delays another day or two I'll probably have to lower the dosage quite a bit to avoid running out.

#44 yoyo

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Posted 25 June 2009 - 08:50 PM

Okay, basically because the dose I want to take is much higher than the prescribed dose I've needed to order pramipexole online from alldaychemist (they were dramatically cheaper than any other source I've seen). In the meantime I'm only taking 0.5mg t.i.d. to avoid getting stuck without and going from a high dose to nothing like I managed to do a few weeks ago. I've been tracking the package and it's been in customs for 64 hours now.

I know it's a tangent, but how long should a package be in customs? Soon it will be 72 hours and that gets me very worried; if it delays another day or two I'll probably have to lower the dosage quite a bit to avoid running out.



it can vary a lot. one time customs held some nardil i ordered for >2 months. then one day it showed up.

#45 Boondock

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Posted 25 June 2009 - 09:36 PM

I know it's a tangent, but how long should a package be in customs? Soon it will be 72 hours and that gets me very worried; if it delays another day or two I'll probably have to lower the dosage quite a bit to avoid running out.


Could take a long time, or could take no time at all. If you experience a delay, perhaps you should order another batch. It might be with you quicker, and in any case you'll receive it all in the end. Costs a bit more but since you're using it in the long-run it'll make no difference.

#46 just1more

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Posted 09 September 2009 - 12:26 AM

Just curious if anyone is still taking Pramipexole and how it's going. I'm interested in it for some of the same reasons as StrangeAeon (improving motiviation and anxiety). I actually received my order from AllDayChemist recently but am a little hesitant to start (not sure on best dosage and worried about side effects).

:just1more:

#47 medievil

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Posted 04 October 2009 - 10:15 AM

Any updates?

#48 Johann

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Posted 02 November 2009 - 09:02 PM

Just curious if anyone is still taking Pramipexole and how it's going. I'm interested in it for some of the same reasons as StrangeAeon (improving motiviation and anxiety). I actually received my order from AllDayChemist recently but am a little hesitant to start (not sure on best dosage and worried about side effects).

:just1more:


This appears to be a promising drug on several fronts. One poster indicated that he may be taking .5 mg three times a day. Will a dose that low work on most? That would probably be how I would do it as I don't want to shell out the money to do 2 or 3 mg/ day.

#49 StrangeAeons

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Posted 03 November 2009 - 01:42 AM

I'm trying to re-integrate pramipexole into my regimen; initially it was with mirtazapine, which potentiates dopamine most everywhere *but* the substantia nigra-- hence it can treat akithisia but exacerbate dyskinesia.
Unfortunately the Remeron (mirtazapine) caused my blood pressure to spike, likely a result of alpha-2 downregulation from MAOI usage synergizing with its alpha-2 antagonism. In its place I'm using galantamine, which should offset the pramipexole's potentially detrimental effects on cognition both as a cholinesterase inhibitor and via dopamine potentiation in the ventral tegmentum; the two principle dopaminergic centers of the brain are the substantia nigra and the ventral tegmentum. I think the greatest benefit (as I need help for residual EPS/movement disorders + attentional/motivational deficits + anhedonia) is achieved by targeting both areas. To be honest, the brief time I was on the Remeron it seemed to do far more for anhedonia than the pramipexole.
Right now I'm just doing 1mg q.d. for the PPX, until the side effects diminish. For me, it caused terrible nausea and general malaise (almost like I had a fever) when first starting it, but the effects subsided within a week of each dosage increase. I would also be cautious going off the stuff, because when I discontinued it a few months back it seemed to trigger some old involuntary movements, likely a form of EPS.

#50 X_Danny_X

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Posted 03 November 2009 - 08:28 PM

i used Prami to get my libido back after taking some anabolic steroids. it repairs and fixes the issue with some help with Cialis or Viagra. it also increase my Human Growth Hormone since i was looking cut up or bigger, my muscles that is.

also for some reason, i couldnt gain any weight. i was exercising to build mass but when i started tooking Prami, i actually lost a few pounds. must speed up the metabolism or the Human Growth Hormone does something from gaining mass.

#51 medievil

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Posted 04 November 2009 - 05:38 PM

Whats the benefit of prami over trivastal?

#52 StrangeAeons

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Posted 05 November 2009 - 05:37 AM

for reasons mentioned above, I want to avoid alpha-2 antagonism. It also has poor bioavailability and half-life relative even to prami.

#53 medievil

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Posted 05 November 2009 - 10:08 AM

for reasons mentioned above, I want to avoid alpha-2 antagonism. It also has poor bioavailability and half-life relative even to prami.

I was thinking whether it would be possible to use trivastal for a few weeks to let the dopamine autoreceptors downregulate and then switch to prami thus avoiding all the side effects. Correct me if i'm wrong tough, i dont know wheter trivastal also causes agonism at the dopamine autoreceptors tough, but it seems logical to me.

#54 caston

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Posted 05 November 2009 - 12:16 PM

Has this been mentioned?

http://en.wikipedia....Adverse_effects

Changes in appetite and weight
Dizziness, lightheadedness, or fainting, especially when standing up (orthostatic hypotension)
Drowsiness
Hallucinations (seeing, hearing, or feeling things that are not there)
Nausea
Insomnia
Twitching, twisting, or other unusual body movements
Unusual tiredness or weakness

#55 X_Danny_X

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Posted 05 November 2009 - 04:49 PM

Has this been mentioned?

http://en.wikipedia....Adverse_effects

Changes in appetite and weight
Dizziness, lightheadedness, or fainting, especially when standing up (orthostatic hypotension)
Drowsiness
Hallucinations (seeing, hearing, or feeling things that are not there)
Nausea
Insomnia
Twitching, twisting, or other unusual body movements
Unusual tiredness or weakness


from reading alot of this in anobolic steroid forums, this happens generally when you overdose and if you just follow the correct amount dosage which is really small daily, you will not experience much of this.

a few folks though just dont think Prami is for them which is basically true for almost any drug.

guys that use steroids usually take a higher dose since they are trying to recover their sex drive because the steroids they take shuts their libido/sex drive down.

#56 StrangeAeons

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Posted 06 November 2009 - 01:35 AM

Firstly, the side effect profile is basically the generic for dopamine agonists, though the piperazine version does bypass the ortthostatic issues (never been a huge issue for me anyways). Secondly, of course all dopamine agonists will have some activity at the autoreceptor, but pramipexole has a selective affinity for the autoreceptors. Thirdly, given the very different of the two drugs I doubt cross-tolerance is going to be easy to gauge or effect.
As mentioned above, you're better off just tapering doses up very slowly (i.e. starting with 0.125mg daily, etc) The whole reason my sleep doctor prescribed me ropinirole the first time he diagnosed me with RLS was because Requip came in little free starter packs with multiple sizes of pills in little blisters for proper dosage escalation.

#57 medievil

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Posted 06 November 2009 - 10:25 PM

Firstly, the side effect profile is basically the generic for dopamine agonists, though the piperazine version does bypass the ortthostatic issues (never been a huge issue for me anyways). Secondly, of course all dopamine agonists will have some activity at the autoreceptor, but pramipexole has a selective affinity for the autoreceptors. Thirdly, given the very different of the two drugs I doubt cross-tolerance is going to be easy to gauge or effect.
As mentioned above, you're better off just tapering doses up very slowly (i.e. starting with 0.125mg daily, etc) The whole reason my sleep doctor prescribed me ropinirole the first time he diagnosed me with RLS was because Requip came in little free starter packs with multiple sizes of pills in little blisters for proper dosage escalation.

I currently am planning a trial with memantine, i know it reduces tolerance to amphetamine, any idea wheter it may block the tolerance that occurs at the dopamine autoreceptors?

#58 Chaos Theory

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Posted 17 January 2010 - 06:11 PM

Anyone manage to have any long-term success with Pramipexole? It seems like everyone over at M&M dropped it due to the sedative sides.

Some of you alluded to a possible repair of dopamine pathways. Is there any evidence for that? I'll even take anecdote at this point, if anyone has managed to stay on it long enough.

I wanted to give it a trial, mostly for the pro-libido effects but I could use an anti-anhedonic in general as well.

#59 OneScrewLoose

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Posted 18 January 2010 - 12:18 AM

This seems like a really interesting drug. However, I would be scared to try it, because of this:

http://www.imminst.o...hl=chaste berry

Chasteberry is a D2 agonist. I don't know if that was the mechanism that made it such a horrible experience, but I don't know if it's worth the risk to find out.

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#60 Chaos Theory

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Posted 18 January 2010 - 05:31 PM

This seems like a really interesting drug. However, I would be scared to try it, because of this:

http://www.imminst.o...hl=chaste berry

Chasteberry is a D2 agonist. I don't know if that was the mechanism that made it such a horrible experience, but I don't know if it's worth the risk to find out.


The only significant side effects I've seen reported from most of the D2 agonists has been sleeping spells, lethargy, or insomnia.




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