# Good experience with requip



## Cydnie (Aug 30, 2010)

I've been going through the threads trying to find out if anyone stuck with requip/ropinirole and read a lot of people stopped because of anhedonia or it didn't work. I'm wondering if anyone had a good experience with it. I was asking my doctor for something else, but he prescribed requip. I wanted something for libido (ssri/snri reduced libido) and read a dopamine agonist might boost my mood as well, and he prescribed this one. I started on a small dose of .25 2 nights, then .5 for 6 nights, but saw a difference in my mood before that and haven't stopped seeing a difference. I also take memantine and had read that that would interfere, but I saw a change in my mood (as well as people around me) within days. I wonder if anyone else has had luck too? My doc wanted me to go up, so I went up last night to 1mg and got so sick, nausea, GI stuff, headache, weakness, flulike feelings, and am not going up that fast again if I even need to go up again. I see no difference in my libido, so maybe I do need to go up (much much slower must be the key) but I don't want to go off because the very obvious success with my mood! I know that some people said it caused anhedonia and memantine interfered, but I can't believe how much better I feel. I have seen some bad side effects (the nausea) and one thing I haven't found scientific evidence for but feel is that it's caused my benzos to stop working for the time being (adaptation phase?) but my mood is so much better and would love to hear if anyone else has has any success? Thanks!


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## crayzyMed (Nov 2, 2006)

Your memantine dose is lower and probably wont really interfere with requip (probably just slow the adaptation).

Be carefull with high doses they could induce anhedonia, sometimes lower is better.


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## mikoy (Aug 12, 2010)

Requip in 0,5 a day works great for my depression, but higher doses makes my anhedonia and depression worse.


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## euphoria (Jan 21, 2009)

I found a scientific basis for memantine inhibiting the adaptation to dopamine agonists (and dopaminergics in general).

*MK-801 prevents alterations in the mesoaccumbens dopamine system associated with behavioral sensitization to amphetamine

*


> Behavioral sensitization to psychomotor stimulants has been shown to be accompanied by a number of alterations in the mesoaccumbens dopamine (DA) system, including DA autoreceptor subsensitivity in the ventral tegmental area (VTA), postsynaptic D1 receptor supersensitivity in the nucleus accumbens (NAc), and augmentation of the DA-releasing effects of stimulants in the NAc. The present study examined whether coadministration of the noncompetitive NMDA antagonist MK-801 with amphetamine, which has been shown to prevent the development of behavioral sensitization to amphetamine, would also prevent these changes in mesoaccumbens DA function. Rats were treated for 5 d with amphetamine according to a regimen known to produce lasting sensitization. *Extracellular single-unit recordings from VTA DA neurons in amphetamine-treated rats, performed after 1 d of abstinence,** revealed robust autoreceptor subsensitivity to DA agonists. This was prevented in rats coadministered MK-801 with amphetamine during the 5 d pretreatment period.* *Recordings from NAc neurons in amphetamine-treated rats demonstrated supersensitivity of D1 receptors to abstinence. **This was also prevented by MK-801 coadministration. * iontophoretic administration of selective agonists when tested after 7 d of Microdialysis studies performed in awake rats after 7 d of abstinence failed to demonstrate augmentation of amphetamine-stimulated DA release in amphetamine-treated rats as compared to water controls, despite the fact that behavioral sensitization was evident in the former group during microdialysis experiments. MK-801 coadministration prevented behavioral sensitization in microdialysis rats but did not alter amphetamine-stimulated DA release. These results suggest (1) NMDA receptor stimulation is required for the development of both autoreceptor subsensitivity in the VTA and postsynaptic D1 receptor supersensitivity in the NAc during repeated amphetamine treatment, (2) these functional changes therefore appear to be closely associated with the development of behavioral sensitization, and (3) a dissociation can be demonstrated between the intensity of amphetamine-stimulated behavioral responses and amphetamine-stimulated DA release in the NAc.


NMDA antagonists prevent the autoreceptor downregulation during amphetamine treatment, and that's required for dopamine agonists to work.

So under this assumption, we can only use acute-acting dopaminergic drugs while on memantine or another NMDA antagonist. I'd guess a similar thing happens with other adaptive processes (e.g. 5-HT1A autoreceptor downregulation), so you might as well extend that to acute-acting drugs in general. That means stuff like amphetamine, which forces dopamine release and can overcome the inhibitory mechanisms. It can't overcome the reduction in TH and thus L-dopa availability, though.


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## crayzyMed (Nov 2, 2006)

euphoria said:


> I found a scientific basis for memantine inhibiting the adaptation to dopamine agonists (and dopaminergics in general).
> 
> *MK-801 prevents alterations in the mesoaccumbens dopamine system associated with behavioral sensitization to amphetamine
> 
> ...


Wich isnt a problem, even on a long term basis if we look at all reports on memantine.


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## crayzyMed (Nov 2, 2006)

> 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 ***** 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 (R)-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.*


Have to look up how they affect other enzym's like TH.


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## crayzyMed (Nov 2, 2006)

> *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
> ...


And yeah it appears NMDA antagonists also facilate TH.


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## euphoria (Jan 21, 2009)

Yeah I also read that study about dizocilpine increasing TH, about a week ago.

You could use amisulpride/sulpiride, or carbidopa + L-dopa to counteract the reduction in TH on amp caused by autoreceptors. Theoretically it'd make amp longer-lasting and more smooth, with only the need for small re-doses during the day.

Also, memantine and opioids increase TH. Maybe it's a reason the opioid + stimulant combo is so popular recreationally (reportedly very euphoric).


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## crayzyMed (Nov 2, 2006)

euphoria said:


> Yeah I also read that study about dizocilpine increasing TH, about a week ago.
> 
> You could use amisulpride/sulpiride, or carbidopa + L-dopa to counteract the reduction in TH on amp caused by autoreceptors. Theoretically it'd make amp longer-lasting and more smooth, with only the need for small re-doses during the day.
> 
> Also, memantine and opioids increase TH. Maybe it's a reason the opioid + stimulant combo is so popular recreationally (reportedly very euphoric).


I personally doubt it would make a any difference tough, altough i'm curious to see your results with sulpiride, i personally expect an initial boost and then the same response due to autoreceptor upregulation (because ppl report a rapid tolerance to those drugs).

I dont think the boost would have anything to do with increased TH activity tough since therapeutic doses of amphetamine cant deplete dopamine, hence i also doubt TH has any impact on the therapeutic response to amp, with chronic or acute use.

Autoreceptor reduced monoamine release can play a role and i do think sulpiride would potentiate amp, but the tolerance issue's with the drug are a real issue. (would be interesting if we could find a way to overcome that).


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## Cydnie (Aug 30, 2010)

not sure if it matters one's non-competitive and one's "uncompetitive"


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