155 replies to this topic

[aLurker]

Yes ive been looking into guanfacine and will probably give it a try.

Only that damn horrible semax price sucks!

What price? sauce??!??! The pharmacy1010 site is deader than disco!

I dont remember it in my head, but the 1% solution was pretty damn horribly expensive.

Pharmacy1010 had 3 ml 1% solution Semax for $195.95... so yeah. Might be cheaper to just go to Russia myself, I wonder if I can get cool stuff cheaply OTC there and take back.

[Thorsten3]

Hey dude I know you mentioned Agomelatine as a possible med you might try. To be honest it increased arousal for me, not just sexually, but my whole body felt hyper. This was uncomfortable after weeks of use and I didn't feel calm or myself after chronic dosing. I wouldn't say it increased anxiety massively but it certainly didn't help at all in that area. For someone like yourself who has documented your issues with pretty severe anxiety it might not be the best thing to go for. Most peeps on the psyconauts group say the same thing. Great for certain depressive conditions but has limited effeciency with anxiety. I only found it useful as an agent for treating anhedonia.

[Knine]

pharmacy1010 is dead, what the, my order wasn't even received, anyone know what to do? eithr get my order or get my money

[Rational Madman]

Problems i'm trying to fix: severe ADHD, OCD and social anxiety:

80mg memantine at this point to see wheter it can actively reverse tolerance while staying at certain substances, also memantine works wonders for my OCD.

AMT: A selective dopamine and serotonine releasing agent, it dramatically improves my condition with far less euphoria of dexedrine (too much euphoria is counterproductive and keeps me inside)/

Dexedrine, because AMT still doesnt fix up mu avoidant behavor, i need a small boost, however dex added to AMT causes way too much euphoria and way too much anxiety.

20 gram piracetam, temporary experiment to see wheter there's some merit to it.
2 gram alcar a day
16mg galantamine a day.
5 mg Nebivolol
8 mg Candesartan

Last 2 i'm trying to counteract the amp anxiety, at this moment AMT and amp are still being inhibited probably because of the memantine adaptation phase, i'm trying to maximize the therapeutic effects and block the euphoria and anxiety.

Being euphoric all day long is fun, but its not the life i want, i want to be free of SA and be outside with my friends all the time, so blocking the counterproductive amp euphoria is a must for me too.

Well see

You have repeatedly claimed that Memantine is doing wonders for your OCD, but at the same time, you're exhibiting unmistakable symptoms of obsessive cognition. Positive studies for this indication are still under review, and for the said indication, Memantine has rarely been incorporated into clinical practice---which by itself should be telling. The same goes for the AMT, which might not be a problematic constituent, but may require additional review. Anecdotally speaking, piracetam has a palpable effect on attentional set-shifting, and maybe exacerbating your preexisting problem with avoidance behavior. Personally, I use it when needed, and I've become convinced that the therapeutic dose is lower than the range that many users administer. Further, didn't you also once confess suffering from a visual hallucination? This strikes me as another reason to reconsider ampakines and Memantine, which may be contraindicated if in the case NMDA receptor behavior is pathologically hypoactive. And again, from anecdotal experience, I found Memantine to be highly dissociative. With all this considered, I think you're fixated on a ostensible issue of amphetamine tolerance that is masquerading as hyperfocus, and with all of this considered, emphatically urge you to cease taking Memantine---especially at such an absurd dose.

Being euphoric for an extended period of time is dysfunctional, and cause for treatment by any rational assessment. And if this is indeed a persistent problem, then it means that whatever you're taking is contributing to mood instability that can no longer be tenable. To some degree, I concur with Animal, but rather, suggest that you reduce your amphetamine dosage, and seriously consider either a mood stabilizer, an antipsychotic, or an antidepressant as an adjunct. Any of these agents alone, or in combination should address some of your concerns. But you need to decide which agent is the culprit, and my position on this matter is already plain.

As for my specific recommendations....
Mood Stabilizers: Lamictal, Lithium, or Depakote
Antidepressants: Remeron, Prozac, Lexapro, Desyrel, or Luvox
Antipsychotics: Zyprexa, Abilify, or Risperdal

Edited by Rol82, 20 October 2010 - 09:52 AM.

[medievil]

Thx for your suggestions.

Hallucionations? Never had them fortionally .


Mood Stabilizers: Lamictal, Lithium, or Depakote (those have all way to many side effects and memantine works perfect as a mood stabiliser for me) Rol why are you so against memantine and do seem to like things like lamictal? wich is another anti glutaminergic but comes with ALOT more side effects!)
Antidepressants: Remeron, Prozac, Lexapro, Desyrel, or Luvox ( Serotonine release > SSRI's wich i'm highly skeptical off, besides that the only utility they could have in my case is OCD but thats allready fixed by the memantine and AMT combo)
Antipsychotics: Zyprexa, Abilify, or Risperdal (No way i'm gonna put one of those in my body, my mum suffers from tardive dyskinesia because of antipsychotics, besides that i dont think they should EVER be used for ppl that arent psychotic )

Cease memantine? No way! I'm the guy that made it popular! The 80mg is an experiment to see wheter it can also reverse tolerance rather then just slowing it. If it doesnt work then i just take my small breaks! Ive been promoting memantine for its anti tolerance properties so id also like to test what its capable off .


As an update nebivolol and candesartan, they worked! They completely abolished all anxiety i used to get from the amphetamine AMT combination.

Without the AMP i'm allmost fixed up except the avoidant behavor, the piracetam definatly doesnt make it worse in my experience, in fact everything that is "stimulating" makes it a bit better like piracetam, cafeine etc.

Reducing the amp dose? Sure thing! perhaps i dont even need it anymore if i find something good to augment the AMT with, otherwise a really small dose would do the trick.

But no way i will put a SSRI, lamictal or any of that other junk in my body, ago looks good, tianeptine looks good too (i wonder how that would work with AMT). Tandospirone, semax etc, there a whole list of things i still want to try.
Perika sparkled my intrest too.

I think ive been on AMT for 1 or 2 months now, id like to stay on it as it improves my condition dramatically, i dont care about the mood boost, the selank completely abolishes that, while the other therapeutic effects remain, stopping amt and then trialling a bunch of SSRI's would be a dramatic waste of time imo, why not build on what allready works?

Memantine and AMT are definatly keepers, amp can be replaced with something differend if it fixes my avoidant behavor.

Edited by medievil, 20 October 2010 - 01:52 PM.

[Knine]

yes i got my order today morning, after thinking i lost everything, haha yes, semax 0.1 and 1.0, ceree 1ml and 5ml, and penotropil,
im hyped to try them out, i think im gonna ask my doctor to give me cere today, and advice on initial dosages?

pharmacy1010 is dead, what the, my order wasn't even received, anyone know what to do? eithr get my order or get my money

[medievil]

Use the search beneath for the dosages, dont remember them all in my head

[aLurker]

yes i got my order today morning, after thinking i lost everything, haha yes, semax 0.1 and 1.0, ceree 1ml and 5ml, and penotropil,
im hyped to try them out, i think im gonna ask my doctor to give me cere today, and advice on initial dosages?

pharmacy1010 is dead, what the, my order wasn't even received, anyone know what to do? eithr get my order or get my money

Awesome! Try Semax 0.1 first and keep us posted! You can always step it up to 1.0 if 0.1 doesn't have an effect!

You know you want to

Edited by aLurker, 20 October 2010 - 02:09 PM.

[Animal]

Because i now discovered AMT wich i beleive is more effecitve then a MAOI (or about the same) however without all the side effects (and i trust the russian documents on amts safety).

I bet you can't reproduce any of these so called 'documents on AMT's safety', because there are none. It was already considered a drug of abuse in 1968, and withdrawn from clinical practice shortly thereafter.

You claim it has two decades of safe clinical application, can you provide evidence for this?

It's a research chemical with no safety data, a history of repeated (and current) recreational abuse and fairly obvious toxicity issues when looking at it's pharmacokinetic analogues. I love how delusional you have become regarding it's safety, it's exactly the same pattern of denial that all drug abusers exhibit.

Like I've already mentioned, it's contraindicated with virtually every potential therapeutic agent that may actually help you find a sustainable management regime. You want to have a hypertensive crisis or serotonin syndrome, then combine it with tianeptine by all means.

[medievil]

It's a research chemical with no safety data, a history of repeated (and current) recreational abuse and fairly obvious toxicity issues when looking at it's pharmacokinetic analogues. I love how delusional you have become regarding it's safety, it's exactly the same pattern of denial that all drug abusers exhibit.

I think ive heared this before, comeone animal! repeating the same line over and over again wont help those delusional individuals! You should know better!

[FunkOdyssey]

What is this releasing agents can't work dogma here? Did you know that bupropion's primary mechanism of action is NE release?

J Clin Psychopharmacol. 2003 Jun;23(3):233-9.
Neurochemical and psychotropic effects of bupropion in healthy male subjects.

Gobbi G, Slater S, Boucher N, Debonnel G, Blier P.

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
Abstract

Bupropion is a weak inhibitor of noradrenaline (NE) and dopamine (DA) reuptake and has no direct action on serotonin (5-HT) neuronal elements. In the rat brain, bupropion suppresses NE neuron firing activity via the activation of alpha(2)-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons. Twenty-five healthy young male volunteers, with no previous history of psychiatric disorders, were randomized to one of four 7-day regimens: placebo, bupropion (150 mg) once daily, bupropion (150 mg) twice a day, and methylphenidate SR (20 mg daily). To assess the activity of the NE reuptake process, the blood pressure response to intravenous tyramine was determined. A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition. Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration, with a decrease serving as an index of 5-HT reuptake blockade. The Profile of Mood States (POMS) scale was used to assess behavioral and psychological changes. Neither bupropion nor methylphenidate altered the tyramine pressor response, in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors. Neither drug modified 5-HT concentrations. However, POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness, agreeability, and energy, whereas 300 mg/day improved only attention. In contrast, methylphenidate improved only energy. These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans. Presumably it enhances synaptic availability of NE by increasing release. Yet, because its behavioral profile is different from that of methylphenidate, it may not share all the biochemical properties of psychostimulants.

PMID: 12826985

Psychopharmacology (Berl). 2001 Apr;155(1):52-7.
Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment.

Dong J, Blier P.

Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100256, Gainesville, FL 32610, USA.
Abstract

RATIONALE: Bupropion is widely used in the treatment of depression and as an anti-craving medication for the cessation of tobacco smoking. Because it is a very weak inhibitor of norepinephrine (NE) and dopamine (DA) reuptake, its mechanisms of action remain to be elucidated.

METHODS: Bupropion was administered subcutaneously via osmotic minipumps over 2 days to determine its effects on the spontaneous firing activity of NE, serotonin (5-HT), and DA neurons in the brain of anaesthetised male Sprague-Dawley rats. This treatment was used in order to obtain levels of the parent compound and its putatively active metabolites that would more adequately reflect the clinical condition than utilizing acute injections.

RESULTS: When given by minipump for 2 days, bupropion produced a dose-dependent attenuation of the mean spontaneous firing NE neurons (7.5 mg/kg per day: 15%; 15 mg/kg per day: 61%; 30 mg/kg per day: 80%) which was reversed by the alpha 2-adrenoceptor antagonist idazoxan. At the highest regimen, the mean firing rate of 5-HT neurons was 100% higher than in control rats, but unaffected in NE-lesioned rats. In contrast, DA neurons in the ventral tegmental area displayed a normal firing rate during the latter bupropion treatment.

CONCLUSIONS: Sustained bupropion administration decreased the firing rate of NE neurons due to an increased activation of their inhibitory somatodendritic alpha 2-adrenoceptors. This effect of the bupropion treatment would be attributable mainly to an enhancement of NE release and not to reuptake inhibition. This contention is based essentially on the observation that NE reuptake blockers leave unaltered the firing rate of 5-HT neurons, whereas bupropion enhanced it via a NE-dependent mechanism. The present study did not put into evidence any DA activity of bupropion at the level of the cell body of mesolimbic/cortical DA neurons at a regimen exerting profound alterations of the firing activity of NE and 5-HT neurons.

PMID: 11374336

Bupropion produces as robust and sustainable an antidepressant effect as any other antidepressant.

In common with some of the drugs Medieval plays with, bupropion also has some potential for and a history of abuse.

Tianeptine, another effective antidepressant, also produces a nice buzz when abused. And amineptine...

So, while I agree a lack of safety data and potential for toxicity are valid reasons someone might not want to use AMT, its mechanism as a monoamine releaser and its potential for abuse are not.

Edited by FunkOdyssey, 20 October 2010 - 06:56 PM.

[aLurker]

*Looks up from notepad*
Thanks Funk, any other abusable drugs you'd like to tell the kids about? :D

[medievil]

Especially when it comes to serotonin releasing agents are far superior, there's a dramatic ammount of ppl not responding to SSRI's wich has been connected to the 5HT1A autoreceptor (atleast in rodents) if we had some releasing agents we had dramatically less treatment resistant patients, but oh well, with the drug abuse phobia, we wont see any in the near future, or if we do they will be actively banned afterwards like amineptine.

[FunkOdyssey]

Especially when it comes to serotonin releasing agents are far superior, there's a dramatic ammount of ppl not responding to SSRI's wich has been connected to the 5HT1A autoreceptor (atleast in rodents) if we had some releasing agents we had dramatically less treatment resistant patients, but oh well, with the drug abuse phobia, we wont see any in the near future, or if we do they will be actively banned afterwards like amineptine.

Even with norepinephrine releasing agents seem to be far superior:

1) SNRI's are similarly or LESS effective at relieving depression than SSRI's (no benefit from NE reuptake inhibition)

2) Selective NE reuptake inhibitors are the crappiest drugs on the planet: strattera (failed antidepressant, tried to repurpose for ADHD), reboxetine (basically a failed antidepressant, lowest efficacy of any antidepressant drug on the market)

3) In contrast, Bupropion is highly effective

4) Combination of an SSRI + bupropion is FAR more effective than an SNRI when they should be very similar if you believed the party line about bupropion acting as an NE reuptake inhibitor

[medievil]

Especially when it comes to serotonin releasing agents are far superior, there's a dramatic ammount of ppl not responding to SSRI's wich has been connected to the 5HT1A autoreceptor (atleast in rodents) if we had some releasing agents we had dramatically less treatment resistant patients, but oh well, with the drug abuse phobia, we wont see any in the near future, or if we do they will be actively banned afterwards like amineptine.

Even with norepinephrine releasing agents seem to be far superior:

1) SNRI's are similarly or LESS effective at relieving depression than SSRI's (no benefit from NE reuptake inhibition)

2) Selective NE reuptake inhibitors are the crappiest drugs on the planet: strattera (failed antidepressant, tried to repurpose for ADHD), reboxetine (basically a failed antidepressant, lowest efficacy of any antidepressant drug on the market)

3) In contrast, Bupropion is highly effective

4) Combination of an SSRI + bupropion is FAR more effective than an SNRI when they should be very similar if you believed the party line about bupropion acting as an NE reuptake inhibitor

Interesting, do you have a source for that? your references for bupe being a releaser allready came in handy, i want to make a thread about this on another forum .

But yeah, release is definatly the way to go, in cases of ADHD i beleive ex dubio mentioned that both ritalin and amphetamine show simular effiacy, so in ADHD dopamine release doenst need to be the preferred option, wonder how that would turn out with depression, anecdotally it appears that amphetamine is far superior for anxiety disorders tough.

[FunkOdyssey]

Maybe not as important with dopamine (amineptine was a reuptake inhibitor). I'll post about SSRI + bupropion in a bit.

[Animal]

In common with some of the drugs Medieval plays with, bupropion also has some potential for and a history of abuse.

Tianeptine, another effective antidepressant, also produces a nice buzz when abused. And amineptine...

So, while I agree a lack of safety data and potential for toxicity are valid reasons someone might not want to use AMT, its mechanism as a monoamine releaser and its potential for abuse are not.

Are you seriously comparing Buproprion and Tianeptine with AMT in terms of abuse/recreational potential? That in itself is enough reason to ignore your post entirely, what nonsense. You're speculating from complete ignorance.

You obviously have no understanding of AMT's pharmacokinetics either if you thinks it's mechanism of action doesn't indicate toxicity/addiction/abuse potential.

[medievil]

You obviously have no understanding of AMT's pharmacokinetics either if you thinks it's mechanism of action doesn't indicate toxicity/addiction/abuse potential.

Abuse potential, definatly!

Addiction? Mental addiction definatly yeah, atleast not as bad as other drugs of abuse, its euphoria is limited in low doses, and being addicted to psychedelics is not as severe as being addicted to stimulants. (you cant trip daily, atleast you can try but that wont even work).

Toxiticy? We know that if we abolish hyperthermia with MDMA we also abolish the toxiticy, alse the ammount of oxidative stress generated plays a keyrole too, it seems obvious that lower doses are less toxic then high doses, therapeutic doses only cause minimal oxidative stress, besides that we dont even have hyperthermia in therapeutic doses.

I dont see why amt is so obvious of a toxin, debatable yes.

[FunkOdyssey]

comparing Buproprion and Tianeptine with AMT in terms of abuse/recreational potential? That in itself is enough reason to ignore your post entirely, what nonsense. You're speculating from complete ignorance.

You obviously have no understanding of AMT's pharmacokinetics either if you thinks it's mechanism of action doesn't indicate toxicity/addiction/abuse potential.

Actually, the meat of my posts in this thread were rebutting your claims regarding releasing agents vs reuptake inhibitors. I think it would be a little unfair to ignore all of the points I made simply because, in your opinion, I haven't accurately gauged the magnitude of AMT's abuse potential (still not clear how this is relevant to efficacy). If we are throwing around terms like complete ignorance and nonsense, look no further than the following:

I also think you need to clarify your understanding on the significant clinical/subjective/chronic difference between a neurotransmitter releasing agent and a re-uptake inhibitor. Re-uptake inhibitors are far better therapeutic agents for extended periods of treatment, with much less abuse potential and sustained mechanisms of action. As opposed to the more rapid and transitory effects of releasing agents which generally come with a crash and minor-moderate toxicity issues.

Edited by FunkOdyssey, 22 October 2010 - 03:14 AM.

[Thorsten3]

Anybody who takes anything is doing so to alter their state of mind. Whether that be for cognitive enhancement, fun, recreationally or for a mood disorder, it's all the same concept. Not all substances have data to backup their safety - aMT we are definitley unsure of to a degree so ultimately it's an individual's decision to take that risk. It's probably highly effective as an anti-depressive but yeah it's those long term issues that would be at the back of my mind.

[medievil]

Currently i'm out of piracetam, and ive dropped my memantine dose to 60mg, wich seems to work without any side effects in my case! The 80mg without piracetam was a bit too much, i felt like i ended up in some weird space mission at times, nonetheless it was an interesting experiment.

Right now i'm on a break of AMT, and this is exactly many of the things i like the most about it, you can just take a break wheneever you want and you dont appear to get any withdrawals or anything else, thus its very easy to return to your baseline state, or stop the AMT trial in case i want to try other things.

You can stop amphetamine right away too but that usually comes with a withdrawal if youv been taking it for some time in a row.

I also ran out of galantamine but plan to readd it with nicotine patches, it provided me with some extra clarity and energy, subtle but a good add on!

I will probably return to AMT after the weekend, time to give my brain a break!

[medievil]

Oh, and normal doses of piracetam this time, the megadosis didnt feel too healthy lol

[Thorsten3]

Oh, and normal doses of piracetam this time, the megadosis didnt feel too healthy lol

At least you never turned into isochroma lol

I wonder how he is getting on, still eating it by the spoonful I reckon

Edited by Thorsten, 22 October 2010 - 02:17 PM.

[medievil]

Ive discovered that at 60mg of memantine /day i feel unusually motivated i attribute this to increased density of several dopamine receptors and increased facilation of dopamine synthesis.

Couple refs:
(PMID: 1382178) Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat.
D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity.

(PMID: 10443547) Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.
The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%.

(PMID: 12832726 Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
We can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain.

(PMID: 10096038) Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP.


And it appears that NMDA antagonists facilate aromatic L-amino acid decarboxylase and tyrosine hydroxylase.

Dizocilpine enhances striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity

Maria Hadjiconstantinoua, b, c, , *, Zvani L. Rossettib, Trina A. Wemlingerb and Norton H. Neffc, b
a Department of Psychiatry, The Ohio State University College of Medicine, 333 W. 10th Avenue, Columbus, OH 43210, USA
b Department of Pharmacology, The Ohio State University College of Medicine, Columbus, OH 43210, USA
c Neuroscience Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Received 31 August 1994; revised 28 November 1994; accepted 6 December 1994. ; Available online 24 January 2003.
Abstract
Dizocilpine administration enhances dopamine metabolism in the rat striatum, nucleus accumbens, olfactory tubercle, and prefrontal cortex. Concomitant with increased metabolism is enhanced tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities in the striatum and increased mRNA for the two enzymes in the midbrain. Activation of dopaminergic neurons may, in part, explain increased locomotor activity in normal animals and the ability of dizocilpine to potentiate the antiparkinsonian action of -3,4-dihydroxyphenylalanine in an animal model.

Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase

Abstract
This study examines the hypothesis that glutamate tonically suppresses the activity of the enzyme aromatic L-amino acid decarboxylase (AADC), and hence the biosynthesis of dopamine, to explain how antagonists of glutamate receptors might potentiale the motor actions of L-DOPA in animal models of Parkinson's disease. A variety of glutamate antagonists were therefore administered acutely to normal rats, which were sacrificed 30–60 min later and AADC activity assayed in the substantia nigra pars reticulate (SNr) and corpus striatum (CS). The NMDA receptor-ion channel antagonists MK 801, budipine, amantadine, memantine and dextromethorphan all caused a pronounced in creased in AADC activity, more especially in the SNr than CS. The NMDA glycine site antagonist ®-HA 966 produced a modest increase in AADC activity in the CS but not SNr, whilst the NMDA polyamine site antagonist eliprodil, the NMDA competitive antagonist CGP 40116 and the AMPA antagonist NBQX were without effect. The results suggest that an increase in dopamine synthesis might contribute to the L-DOPA-facilitating actions of some glutamate antagonists.

This would make memantine an interesting candidate for people that have motivational problems, i would expect the effects to last since NMDA antagonism also increases dopamine receptor mRNA expression, most benefits might even come from the increased dopamine sensivity.

[Thorsten3]

Ive discovered that at 60mg of memantine /day i feel unusually motivated i attribute this to increased density of several dopamine receptors and increased facilation of dopamine synthesis.

Couple refs:
(PMID: 1382178) Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat.
D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity.

(PMID: 10443547) Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.
The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%.

(PMID: 12832726 Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
We can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain.

(PMID: 10096038) Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP.


And it appears that NMDA antagonists facilate aromatic L-amino acid decarboxylase and tyrosine hydroxylase.

Dizocilpine enhances striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity

Maria Hadjiconstantinoua, b, c, , *, Zvani L. Rossettib, Trina A. Wemlingerb and Norton H. Neffc, b
a Department of Psychiatry, The Ohio State University College of Medicine, 333 W. 10th Avenue, Columbus, OH 43210, USA
b Department of Pharmacology, The Ohio State University College of Medicine, Columbus, OH 43210, USA
c Neuroscience Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Received 31 August 1994; revised 28 November 1994; accepted 6 December 1994. ; Available online 24 January 2003.
Abstract
Dizocilpine administration enhances dopamine metabolism in the rat striatum, nucleus accumbens, olfactory tubercle, and prefrontal cortex. Concomitant with increased metabolism is enhanced tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities in the striatum and increased mRNA for the two enzymes in the midbrain. Activation of dopaminergic neurons may, in part, explain increased locomotor activity in normal animals and the ability of dizocilpine to potentiate the antiparkinsonian action of -3,4-dihydroxyphenylalanine in an animal model.

Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase

Abstract
This study examines the hypothesis that glutamate tonically suppresses the activity of the enzyme aromatic L-amino acid decarboxylase (AADC), and hence the biosynthesis of dopamine, to explain how antagonists of glutamate receptors might potentiale the motor actions of L-DOPA in animal models of Parkinson's disease. A variety of glutamate antagonists were therefore administered acutely to normal rats, which were sacrificed 30–60 min later and AADC activity assayed in the substantia nigra pars reticulate (SNr) and corpus striatum (CS). The NMDA receptor-ion channel antagonists MK 801, budipine, amantadine, memantine and dextromethorphan all caused a pronounced in creased in AADC activity, more especially in the SNr than CS. The NMDA glycine site antagonist ®-HA 966 produced a modest increase in AADC activity in the CS but not SNr, whilst the NMDA polyamine site antagonist eliprodil, the NMDA competitive antagonist CGP 40116 and the AMPA antagonist NBQX were without effect. The results suggest that an increase in dopamine synthesis might contribute to the L-DOPA-facilitating actions of some glutamate antagonists.

This would make memantine an interesting candidate for people that have motivational problems, i would expect the effects to last since NMDA antagonism also increases dopamine receptor mRNA expression, most benefits might even come from the increased dopamine sensivity.

So suppression of glutamte via NMDA increases domapine synthesis?

I remember I got these effects @20mg, but the effects didn't last. It was a realy cool feeling though. I just wanted to get out there and live my life when I was feeling like that. Then its effects turned into that of being 'bubble wrapped' so dissapointingly didn't last. Pretty sure that would happen eventually at any dose. If those effects did last, trust me I would still be on memantine!

[medievil]

So suppression of glutamte via NMDA increases domapine synthesis?

I remember I got these effects @20mg, but the effects didn't last. It was a realy cool feeling though. I just wanted to get out there and live my life when I was feeling like that. Then its effects turned into that of being 'bubble wrapped' so dissapointingly didn't last. Pretty sure that would happen eventually at any dose. If those effects did last, trust me I would still be on memantine!

My response seems a bit differend to yours tough, memantine has allways been neutral for me, never caused much effects except decreased my OCD, it also doesnt feel dopaminergic now just notice the increased motivation, the fact that my response seems much milder compared to yours and i never got the bubble feeling, makes me a bit optimistic that its gonna stay, but lets see in a few days! .

It doesnt really make me want to live my life, still wasting time behind my computer, except with motivation for the important things this time!

Edited by medievil, 22 October 2010 - 04:37 PM.

[medievil]

So suppression of glutamte via NMDA increases domapine synthesis?

yeah, NMDA antagonism increases dopamine synthesis.

[medievil]

Hey thorsten,

I was thinking that the benefits you noticed came from increased dopamine synthesis, however they pooped out due to dopamine receptor downregulation, perhaps by pushing memantine high enough it starts upregulation dopamine and then prevents tolerance to itself so at higher doses the feeling may last. Just an idea.

Altough you where also gonna send me your memantine, but you can keep it if you want to do some more experimentation .

Edited by medievil, 22 October 2010 - 06:54 PM.

[Thorsten3]

Hey thorsten,

I was thinking that the benefits you noticed came from increased dopamine synthesis, however they pooped out due to dopamine receptor downregulation, perhaps by pushing memantine high enough it starts upregulation dopamine and then prevents tolerance to itself so at higher doses the feeling may last. Just an idea.

Altough you where also gonna send me your memantine, but you can keep it if you want to do some more experimentation .

Would that work? If I could tolerate the body load then it would be something I'd be willing to try. I eventually went up to 30mg whilst I was on it and adapted mentally to the effects but I remember the dirty feeling that accompanied it. I would not be happy popping any more than that per day. That's cool you can still have the memantine

[Rational Madman]

Thx for your suggestions.

Hallucionations? Never had them fortionally .


Mood Stabilizers: Lamictal, Lithium, or Depakote (those have all way to many side effects and memantine works perfect as a mood stabiliser for me) Rol why are you so against memantine and do seem to like things like lamictal? wich is another anti glutaminergic but comes with ALOT more side effects!)
Antidepressants: Remeron, Prozac, Lexapro, Desyrel, or Luvox ( Serotonine release > SSRI's wich i'm highly skeptical off, besides that the only utility they could have in my case is OCD but thats allready fixed by the memantine and AMT combo)
Antipsychotics: Zyprexa, Abilify, or Risperdal (No way i'm gonna put one of those in my body, my mum suffers from tardive dyskinesia because of antipsychotics, besides that i dont think they should EVER be used for ppl that arent psychotic )

Cease memantine? No way! I'm the guy that made it popular! The 80mg is an experiment to see wheter it can also reverse tolerance rather then just slowing it. If it doesnt work then i just take my small breaks! Ive been promoting memantine for its anti tolerance properties so id also like to test what its capable off .


As an update nebivolol and candesartan, they worked! They completely abolished all anxiety i used to get from the amphetamine AMT combination.

Without the AMP i'm allmost fixed up except the avoidant behavor, the piracetam definatly doesnt make it worse in my experience, in fact everything that is "stimulating" makes it a bit better like piracetam, cafeine etc.

Reducing the amp dose? Sure thing! perhaps i dont even need it anymore if i find something good to augment the AMT with, otherwise a really small dose would do the trick.

But no way i will put a SSRI, lamictal or any of that other junk in my body, ago looks good, tianeptine looks good too (i wonder how that would work with AMT). Tandospirone, semax etc, there a whole list of things i still want to try.
Perika sparkled my intrest too.

I think ive been on AMT for 1 or 2 months now, id like to stay on it as it improves my condition dramatically, i dont care about the mood boost, the selank completely abolishes that, while the other therapeutic effects remain, stopping amt and then trialling a bunch of SSRI's would be a dramatic waste of time imo, why not build on what allready works?

Memantine and AMT are definatly keepers, amp can be replaced with something differend if it fixes my avoidant behavor.

For the mood stabilizers and antipsychotics, I would only endorse low therapeutic doses as a base, and as a last resort if antidepressant therapy fails to relieve symptoms. My problem with Memantine is its relative affinity for NMDA receptors, which I believe is more likely to create problems in cases where NMDA receptor hypoactivity might be pathologically relevant. And by using ampakines, there is the risk of exacerbating this imbalance. As I've stated before, excess glutamate may be problematic in certain regions, but not necessarily in every region. So low doses of mood stabilizers may be more of a delicate approach. As for the use of antipsychotics, I'm wondering if some of your D2 and D3 receptors are hyperactive (or being overstimulated), and if this is the case, you might benefit from a low dose of an antipsychotic as an adjunct to other dopaminergics. These are, of course, not the most palatable options, but they need to be considered if your current cocktail is not working to your satisfaction.

Edited by Rol82, 23 October 2010 - 11:04 PM.