86 replies to this topic

[Cappa]

From wiki:

Several unusual adverse effects of pramipexole (and related D3-preferring dopamine agonist medications such as ropinirole) may include compulsive gambling, hypersexuality, and overeating,[10] even in patients without any prior history of these behaviours.[11] Other compulsive behaviors, such as excessive shopping and even cross-dressing, have been reported.[12] These side effects are thought to be linked to the D3 activity of pramipexole, as D3 receptors are heavily expressed in brain regions involved in mood, behavior, and reward.[13]

I'm guessing that anyone who starts cross-dressing while taking this already has an unconventional gender identity and the Pramipexole merely made them less inhibited.

Edited by Cappa, 18 January 2010 - 05:53 PM.

[FunkOdyssey]

It is absolutely capable of doing weird/bad things to your personality and behavior -- that is the main reason I am wary of pramipexole and dopamine agonists in general now.

[Ben]

It is absolutely capable of doing weird/bad things to your personality and behavior -- that is the main reason I am wary of pramipexole and dopamine agonists in general now.

Wouldn't anything that increases the degree to which dopamine receptors are activated have this same effect? E.g.: Deprenyl?

Edited by Ben - Aus, 19 January 2010 - 03:08 PM.

[medievil]

I beleive that any change in behaver can be avoided if the doses are kept low enough, its probably caused by exces stimulation of the D receptors.

[OneScrewLoose]

It is absolutely capable of doing weird/bad things to your personality and behavior -- that is the main reason I am wary of pramipexole and dopamine agonists in general now.

Wouldn't anything that increases the degree to which dopamine receptors are activated have this same effect? E.g.: Deprenyl?

Not even. Heck, drugs that even work on the exact same thing can have different effects (i.e. Ritalin and Cocaine). Always keep in mind that right now we are in the stone age of receptor chemistry science, and not to make broad-based assumptions for any neurotransmitter. But, it's more specifically the D3 agonism that causes the personality-changing/obsessive effects, not just dopamine in general.

[browser]

So, Mirapex is starting to come into serious consideration for me for psychiatric purposes. What's the availability?

Its available from the usual overseas sources, about $20-$30 for a month's supply depending on dose, made by Sun Pharmaceuticals.

Would someone kindly PM me with reliable overseas (outside of USA) sources of Miraplex? When I google Miraplex I get what look like scam sites offering "generic" Miraplex.

Thanks.

[FunkOdyssey]

browser: No one can PM you because you have disabled your ability to receive private messages from other users.

[medievil]

It is absolutely capable of doing weird/bad things to your personality and behavior -- that is the main reason I am wary of pramipexole and dopamine agonists in general now.

Wouldn't anything that increases the degree to which dopamine receptors are activated have this same effect? E.g.: Deprenyl?

Not even. Heck, drugs that even work on the exact same thing can have different effects (i.e. Ritalin and Cocaine). Always keep in mind that right now we are in the stone age of receptor chemistry science, and not to make broad-based assumptions for any neurotransmitter. But, it's more specifically the D3 agonism that causes the personality-changing/obsessive effects, not just dopamine in general.

Dopamine itself is a full D3 agonist, so if prami causes changes in behavor anything that increases dopamine can.

Anyway, D3 and D2 are connected to social succes, so prami could have the most benefit for the socially anxious.

[Chaos Theory]

I decided to give this a trial. I'm on day 3 @ .25mg before bed. No complaints so far, though I didn't sleep well at all the first night. The following two I took 750mg passifloria extract which seemed to help quite a bit.

Though the half-life is short, supposedly that isn't representative of the drug's life in the body after chronic use due to accumulation in tissues. At least thats some broscience I read on another board... Once daily dosing does seem to improve my mood the following day, which may or may not be related to deeper sleep.

This article on it's effectiveness in fibromyalgia sheds some more light on it.

http://www.medscape....warticle/538007
"The rationale behind using a dopamine agonist in fibromyalgia is not well worked out, but the leading theory—at least in my mind—is that these drugs act to decrease the autonomic arousal that fragments deep sleep," Holman explains. Dopamine in the brain affects a variety of functions, including pain, and the D3 dopamine receptors are found in the mesolimbic area, which is the part of the brain that inhibits arousal coming from the brain stem. The theory is that the D3 agonist at higher doses increases postsynaptic neurotransmission, possibly in the hippocampus, and this increases inhibition of the arousal, but he points out that the theory is still controversial—"it's highly speculative but intriguing," he comments.

[medievil]

Interesting, keep us updated!

[Chaos Theory]

Interesting, keep us updated!

Update: I think I see why nobody stuck it out with this stuff.

I'm on day 4 and while I generally feel alright in the morning, as the day wears on I feel increasingly more lethargic and out of it. I've also experienced a bit of what Funk was alluding to with the effects on personality.

I wanted to stick it out and give it a fair trial but I have too much going on right now to spend any significant amount of time feeling lethargic while I adjust to the pramipexole.

[medievil]

I'm starting to think that both requip and trivastal are far better options as they seem to have alot more positive reviews, everyone seems to give up on prami..


Especially trivastal seems good as its very benign and has many good reviews (ive been trying big doses on the first day with trivastal several times without any ill effects, no nausia, sedation or nothing.)
Seems like a much better option.

Edited by medievil, 27 February 2010 - 06:09 AM.

[Logan]

I'm starting to think that both requip and trivastal are far better options as they seem to have alot more positive reviews, everyone seems to give up on prami..


Especially trivastal seems good as its very benign and has many good reviews (ive been trying big doses on the first day with trivastal several times without any ill effects, no nausia, sedation or nothing.)
Seems like a much better option.

How do you feel on trivastal??

[medievil]

I'm starting to think that both requip and trivastal are far better options as they seem to have alot more positive reviews, everyone seems to give up on prami..


Especially trivastal seems good as its very benign and has many good reviews (ive been trying big doses on the first day with trivastal several times without any ill effects, no nausia, sedation or nothing.)
Seems like a much better option.

How do you feel on trivastal??

My mood seems a bit down on it, as expected as dopaminergic transmission will drop the first few days, but other then that NO side effects AT ALL, no nausia, sedation or any other of those side effects what make ppl give up on prami.
Most experiences on it are positive too, i made a collection of them on mind&muscle.
http://www.mindandmu...mp;hl=trivastal

Ive not taking it long enough yet for the real benefits to show up.

[medievil]

NVM the trivastal, it appears to be a partional agonist, wich explains the lack of side effects but would also mean its far from as effective as prami.

Better to stay on prami.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.
Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ.

Department of Psychopharmacology, Institut de Recherches Servier, Centre de Recherches de Croissy, 125 chemin de Ronde, 78290 Croissy/Seine, Paris, France.
The accompanying multivariate analysis of the binding profiles of antiparkinson agents revealed contrasting patterns of affinities at diverse classes of monoaminergic receptor. Herein, we characterized efficacies at human (h)D(2SHORT(S)), hD(2LONG(L)), hD(3), and hD(4.4) receptors and at halpha(2A)-, halpha(2B)-, halpha(2C)-, and halpha(1A)-adrenoceptors (ARs). As determined by guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, no ligand displayed "full" efficacy relative to dopamine (100%) at all "D(2)-like" sites. However, at hD(2S) receptors quinpirole, pramipexole, ropinirole, quinerolane, pergolide, and cabergoline were as efficacious as dopamine (E(max)100%); TL99, talipexole, and apomorphine were highly efficacious (79-92%); piribedil, lisuride, bromocriptine, and terguride showed intermediate efficacy (40-55%); and roxindole displayed low efficacy (11%). For all drugs, efficacies were lower at hD(2L) receptors, with terguride and roxindole acting as antagonists. At hD(3) receptors, efficacies ranged from 33% (roxindole) to 94% (TL99), whereas, for hD(4) receptors, highest efficacies (approximately 70%) were seen for quinerolane, quinpirole, and TL99, whereas piribedil and terguride behaved as antagonists and bromocriptine was inactive. Although efficacies at hD(2S) versus hD(2L) sites were highly correlated (r = 0.79), they correlated only modestly to hD(3)/hD(4) sites (r = 0.44-0.59). In [(35)S]GTPgammaS studies of halpha(2A)-ARs, TL99 (108%), pramipexole (52%), talipexole (51%), pergolide (31%), apomorphine (16%), and quinerolane (11%) were agonists and ropinirole and roxindole were inactive, whereas piribedil and other agents were antagonists. Similar findings were obtained at halpha(2B)- and halpha(2C)-ARs. Using [(3)H]phosphatidylinositol depletion, roxindole, bromocriptine, lisuride, and terguride displayed potent antagonist properties at halpha(1A)-ARs. In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D(2)-like receptor and alpha(1)/alpha(2)-AR, actions, which likely contribute to their contrasting functional profiles.

[medievil]

With the use of domperidone and LDOPA we can get the positive effects of pramipexole right away.

Ldopa fully counteracts the decreased dopaminergic transmission and would help desentisize the autoreceptors so that after the adaption period LDOPA can be stopped while the benefits of prami remain.

domperidone prevents the desentisation of D receptors in the puking centers tough and needs to be taken all the time with prami, so thats a bit of a downside, but the combo could help figure out how prami would help you quickly.

Edited by medievil, 28 February 2010 - 07:36 PM.

[togameru]

It is absolutely capable of doing weird/bad things to your personality and behavior -- that is the main reason I am wary of pramipexole and dopamine agonists in general now.

You've never gone to the trouble of giving some examples of these adverse changes in personality and behaviour that you keep mentioning. I understand that it's not rational to assume that others would necessarily experience what you have, but all the same I would like to know what the pramipexole did to you; what you regard as "weird/bad" might be agreeable/desirable to me.

Did the drug at least increase your hedonic tone?

I find myself kind of annoyed by those who used the drug for a considerable period of time but were remiss enough not to report their experiences. Where does that leave those who are interested in trying it? If the drug only makes one miserable, weird, and vaguely psychotic, that's something these people are going to have to experience themselves because they were not adequately forewarned by those who could easily have done so.

Edit: I wouldn't mind having you PMing your source, as well. I'm hoping I haven't disaffected you with my apparent curtness to the point of discouraging you from doing so.

Edited by togameru, 07 March 2010 - 01:48 AM.

[togameru]

With the use of domperidone and LDOPA we can get the positive effects of pramipexole right away.

Ldopa fully counteracts the decreased dopaminergic transmission and would help desentisize the autoreceptors so that after the adaption period LDOPA can be stopped while the benefits of prami remain.

domperidone prevents the desentisation of D receptors in the puking centers tough and needs to be taken all the time with prami, so thats a bit of a downside, but the combo could help figure out how prami would help you quickly.

This is just about the worst idea I've ever come across. The rate-limiting steps in dopamine synthesis are the phenylalanine -> tyrosine step and tyrosine -> levodopa step. There's no room for error when dosing levodopa. And I'm not sure what the point of the domperidone is in light of the fact that it doesn't cross the blood brain barrier readily and pramipexole-induced nausea seems to be quite rare at the doses at which people are taking it. There's another problem with the domperidone: some people are using the pramipexole to increase libido, and even though domperidone preponderantly acts peripherally, it's still able to dramatically increase prolactin levels. Prolactin decreases the sensitivity of D2 receptors, if I'm not mistaken. I've also heard that levodopa is converted into 6-hydroxydopamine, which is extremely toxic to the dopamine-producing neurons in the substantia nigra.

Additionally, you ignore the possibility that some of the beneficial effects of pramipexole may be due the inhibitory effect on dopaminergia mediated by D3 autoreceptors (e.g. the neurogenesis and synaptogenesis reported in a number of studies might occur in the earlier stages of treatment when the autoreceptors have yet to fully desnsitize.)

Edited by togameru, 07 March 2010 - 01:44 AM.

[medievil]

With the use of domperidone and LDOPA we can get the positive effects of pramipexole right away.

Ldopa fully counteracts the decreased dopaminergic transmission and would help desentisize the autoreceptors so that after the adaption period LDOPA can be stopped while the benefits of prami remain.

domperidone prevents the desentisation of D receptors in the puking centers tough and needs to be taken all the time with prami, so thats a bit of a downside, but the combo could help figure out how prami would help you quickly.

This is just about the worst idea I've ever come across. The rate-limiting steps in dopamine synthesis are the phenylalanine -> tyrosine step and tyrosine -> levodopa step. There's no room for error when dosing levodopa. And I'm not sure what the point of the domperidone is in light of the fact that it doesn't cross the blood brain barrier readily and pramipexole-induced nausea seems to be quite rare at the doses at which people are taking it. There's another problem with the domperidone: some people are using the pramipexole to increase libido, and even though domperidone preponderantly acts peripherally, it's still able to dramatically increase prolactin levels. Prolactin decreases the sensitivity of D2 receptors, if I'm not mistaken. I've also heard that levodopa is converted into 6-hydroxydopamine, which is extremely toxic to the dopamine-producing neurons in the substantia nigra.

Additionally, you ignore the possibility that some of the beneficial effects of pramipexole may be due the inhibitory effect on dopaminergia mediated by D3 autoreceptors (e.g. the neurogenesis and synaptogenesis reported in a number of studies might occur in the earlier stages of treatment when the autoreceptors have yet to fully desnsitize.)

I agree that it was a stupid idea, was not thinking when i posted that.

[chroncile]

So is anyone here still using Pramipexole? If so, how long were you on it for and did you have to cycle it?

[abelard lindsay]

You should all be aware that this drug has some side effects:

http://www.lawyersan...ve-6-15863.html

http://www.innovatio...e-masturbation/

[SocietyOfMind]

You've never gone to the trouble of giving some examples of these adverse changes in personality and behaviour that you keep mentioning. I understand that it's not rational to assume that others would necessarily experience what you have, but all the same I would like to know what the pramipexole did to you; what you regard as "weird/bad" might be agreeable/desirable to me.

I don't think it's just one person:

articles.latimes.com/2006/may/23/science/sci-parkinsons23

[the_apollo]

The fatigue is due to temporary reductions in firing rate of NE and DA neurons. This effect is transient and disappears with continued use as autoreceptors are desensitized. This is discussed in more detail in the link I provided above.

There seems to be very little information on that, so i have to ask; How long time does that "temporary reductions in firing rate.." take before the autoreceptors is desensitized and the positive effects of pramipexole is starting,,?

[medievil]

Togheter with a benzamide ap in doses selective for the presynaptic neurons i could take high doses of pramipexole straight away, but as i only got a low dose of prami i took it all in one evening i cant really elaborate on its effects, definatly avoided the negatives and the need to slowly taper up.

[nowayout]

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.

i would be interested also in any updates. Sedative sides I would love, to be honest. What happened to the initial enthusiasm, and is it safe long term?

Edited by nowayout, 17 September 2013 - 08:30 PM.

[Milkyway]

Is anyone afraid of the legal consequences of ordering Pramipexole as a supplement or does anyone have any experience with that? 

[stefdude]

Can someone help me with this?I am trying to follow the protocol of Fawcett's study of initial goal of 2mg once a day.I've reached 1.5mg and my autoreceptors have probably been downregulated because I went from mild nausea and heavy sleepiness after dosing to not be ablw to sleep properly.

This looks like a lot to take at once.Would it be the same to take 3x0.5mg or 2x1mg?Anyone with experience?

I am trying to increase my motivation to help my chronic fatigue syndrome.