11 replies to this topic

[Nooby]

Hi this is my first post!

I have followed these boards for some time. I have taken the decision recently to try and tackle my persisting anhedonia and last week I recieved my order of trivastal retard. I'm sure most of you are aware of its pharmacology. It's a pretty weak DA agonist with adrenergic antagonist properties hence its adaption phase is reportably more pleasant than other DA based agonist drugs. I would consider it a nootropic of sorts due to its apparant cognition enhancing effects and its supposed positive effects on mood (which in itself is a nootropic)

But I am currently having second thoughts on whether I even want to emabark on this journey. I am worried that long term administration of a dopamine agonist will come with drawbacks eventually or receptor downregulation. Surely this would be the case for all dopamine agonists? So ropinirole, mirapex to name but a few would also eventually 'poop'. Or am I missing something here?

I have read that Memantine can prevent tolerance to amphetamines but would it also be useful for other types of drugs specifically dopamine agonists?

I would appreciate advice here as i have pretty basic limited understanding. If anyone would care to shed some light on how the pharmacology is likely to work I would be delighted to hear.

[medievil]

I have succesfully taken trivastal a while to counteract my anhedonia (altough very short term as i ran out) its a week dopamine agonist (only has an intrinsic acivity of 50% or something) its also a D4 antagonist.

I dont know how much tolerance would be an issue with trivastal.

I have 2 friends that have taken pramipexole for social anxiety, one for several months without any loss in effiacy, however he has been having severe withdrawal problem, currently at he's 5th attempt to quit te drug, altough its not as bad for everyone, and i also beleive that with trivastal it would be less of an issue since its only a partional agonist. (Both developped severe apathy and anhedonia on pramipexole by the way, only trivastal has some potential in the anhedonia department, ropinirole perhaps too at lower doses (found 1 anecdotal report saying it helped anhedonia).

Memantine wont help with dopamine agonist tolerance as NMDA antagonism upregulates both the presynaptic as the postsynaptic receptors, my friend that took prami for several months reported a complete reversal of the adaptation after raising he's memantine dose.

For anhedonic issue's i would gues that lisuride shows most potential in that regard as its also a potent 5HT2A agonist wich would facilate dopamine release, it also lacks most of the D3 agonism wich could be an explanation for pramipexole's induced anhedonia, since D3 seems to have an opposing role on reward (atleast regarding CPP or condiotioned place preference) but its debetable wheter that actually is a measure of reward.

Anyway, i definatly think trivastal is worth a try for anhedonia.

[chrono]

@Nooby: Welcome! If you decide to try it, I hope you'll keep a good log here for us. I'm interested in the potential of dopamine agonists as well, and would love to have more good experience reports to draw from.

Memantine wont help with dopamine agonist tolerance as NMDA antagonism upregulates both the presynaptic as the postsynaptic receptors, my friend that took prami for several months reported a complete reversal of the adaptation after raising he's memantine dose.

Don't I recall that someone thought the looong adaptation period of pramipexole was a confounding factor in that experience? Or do you think it's generally applicable to all agonists?

[medievil]

What do you mean with a confouding factor? It took him a full months before he was adapted to prami and the benefits appeared, he took it for a few months and the he added in 40mg of memantine and the adaptation period of pramipexole completely reversed back to when he took prami the first time.

[Pike]

memantine is also a D2 receptor agonist.

[chrono]

What do you mean with a confouding factor? It took him a full months before he was adapted to prami and the benefits appeared, he took it for a few months and the he added in 40mg of memantine and the adaptation period of pramipexole completely reversed back to when he took prami the first time.

I guess I meant, does travistal have an adaptation process with the same characteristics, or might this "resetting" have been due in part to something unique to the pharmacology of prami. Sorry if this is a naive question, but I haven't researched either very thoroughly.

[medievil]

What do you mean with a confouding factor? It took him a full months before he was adapted to prami and the benefits appeared, he took it for a few months and the he added in 40mg of memantine and the adaptation period of pramipexole completely reversed back to when he took prami the first time.

I guess I meant, does travistal have an adaptation process with the same characteristics, or might this "resetting" have been due in part to something unique to the pharmacology of prami. Sorry if this is a naive question, but I haven't researched either very thoroughly.

All dopamine agonists initially lower dopamine due to activation of the autoreceptors, causing a net antagonistic effect (the opposite of what we would want to get) over time they desentize and the dopamine agonist activates the postsynaptic receptors without the initial lowering effect, thus having a agonistic effect. This is pretty much the case with all dopamine agonists, altough trivastal has a weak intrinsic activity, it probably doesnt cause the same lowering in dopamine at first (due to only 50% activation of the autoreceptors as opposed to full agonism) and may therefor show some effects right away, as it did for me.

[NR2(x)]

I would not use a compound that displays dopamine 4 antagonist properties because positive function of these receptor is vital for health and wealth. I have heard these receptor described as the play receptor, which signifies there importants in adaptive learning and synaptic plasticity.
Dopamine 4 agonist have been shown in animal models to be highly efficious in treating ADD.
Under-Methylation is a strong syptom of many cognitive diseases and the D4 receptor is tightly tied to this pathway through insulin-like growth factors.

Taking drugs that modulate dopamine is a highly efficious method of cognitive enhancment. Typically the effect curve is inverse parabolic, meaning that some is good, while alot is bad.
Ergoloids look interesting

THe commonalities of chemcial structure between pramipexole and modafinil look interesting

[nowayout]

Mucuna Pruriens is big in some circles. I know of guys who have apparently been using Mucuna with good results long term, but taking it each other day only to limit desensitization.

I have experimented with it, but it never did a thing for me.

[chrono]

Mucuna Pruriens is big in some circles. I know of guys who have apparently been using Mucuna with good results long term, but taking it each other day only to limit desensitization.

L-DOPA is an immediate precursor to dopamine, so not technically an agonist. At least, I don't think the plant has any other mechanisms. I use it occasionally, and it has for me a strong effect, though somewhat inconsistent.

[Pike]

for what it's worth, i'd like to throw in my suggestion to those taking L-Dopa to seriously consider intaking some green-tea extract with a good amount of EGCG in it. L-Dopa is the direct precursor to dopamine and most of those taking L-Dopa are doing so for it's boost to your central nervous system. however, it's pretty easy for L-Dopa to metabolize itself into dopamine peripherally and that can be unpleasant, as well as have its side effects in the long term. EGCG is a natural peripheral aromatic-l-amino acid decarboxylase inhibitor and can really help keeping most of that l-dopa metabolization in the central nervous system. so, aside from green tea being mega healthy, now your peripheral nervous system is left in the green and your L-Dopa is going a longer way.

however, just out of personal preference, even though i DO use GTE, my amino acid of choice for dopamine is DL-PA. i'm not entirely sure how true all of the hype about D-PA is, but it works well for me.

[John Barleycorn]

I guess I meant, does travistal have an adaptation process with the same characteristics, or might this "resetting" have been due in part to something unique to the pharmacology of prami.

There have been suggestions on another board that there may have been something rather unique to the pharmacology of the individual concerned! Either that, or the fact that he (?) was taking so many substances simultaneously that it was a bit difficult to keep up.

In theory, low doses of prami et al should target the autoreceptors only and eventually should make one more responsive to life's little pleasures. The big drawback is the unpleasant adjustment period. At that point, higher doses may be pleasurable in themselves, but it is debatable whether that is sustainable.

Ergot-based agonists have serious peripheral side-effect problems.

M. Pruriens personally makes me sick, but YMMV.