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The Use of Dopamine Agonists in Psychiatry

T

Truthometer

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Ropinirole

Ropinirole is a D2, D3, and D4 dopamine receptor agonist. Its affinity for D3 receptors is 20 times greater than for D2 receptors [1]. Ropinirole is useful in treating SSRI-induced sexual dysfunction [2]. Ropinirole could be useful as an adjunctive treatment for treatment-resistant depression [3] Ropinirole is also useful in treating negative symptoms of schizophrenia [4]. Ropinirole is primarily used in the treatment of Parkinson's disease.

Pramipexole

Pramipexole is also primarily used in the treatment of Parkinson's disease. Pramipexole is also a D2-like receptor agonist: D2, D3, and D4, with the following intrinsic activities:

D2L [70%] = high partial agonist
D2S [130%] = superagonist
D3 [70%] = high partial agonist
D4 [42%] = partial agonist

Pramipexole has highest affinity for D3 receptors. Pramipexole is also useful as an adjunctive treatment for depression, anhedonia [5], and negative symptoms.

Cabergoline

Cabergoline is a D1, D2, D3, and D4 agonist. Cabergoline also has agonistic activity on 5HT1A and 5HT2A receptors. It is used to lower prolactin levels and treat SSRI-induced sexual dysfunction (low libido, anorgasmia) [6]. It can be used as an aphrodisiac, as it boosts libido, intensifies orgasms, and enhances sexual performance (shortens the refractory period after an orgasm) [7], that is, with Cabergoline people can skip the post orgasm hangover.
 
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Bromocriptine

Bromocriptine is a potent agonist at dopamine D2 receptors and various serotonin receptors. It also inhibits the release of glutamate. Bromocriptine is used to treat hyperprolactinaemia (high prolactin levels), neuroleptic malignant syndrome, and Parkinson's disease [1]. Bromocriptine is also used to treat infertility, hypogonadism and diabetes II [1]. Bromocriptine has also been found to reduce negative symptoms of schizophrenia [2].

Pharmacodynamics of Bromocriptine:


  • Dopamine D1 family
    • D1 (Ki=682 nM)
    • D5 (Ki=496 nM)
  • Dopamine D2 family
    • D2 (Ki=2.96 nM)
    • D3 (Ki=5.42 nM)
    • D4 (Ki=328 nM)
  • Serotonin 5-HT
Note: Ki = dissociation constant. The smaller the Ki value the stronger the affinity (chemical binding strength).
 
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I've only tried bromocriptine & cabergoline, both for depression & to try to treat SSRI induced anorgasmia (so alone & combined with fluoxetine). Both felt very similar & made feel horrible, very dysphoric, plus headache & nausea. I was not impressed, to say the least. I personally seem to only respond well to DA releasers like amphetamine, with little effect from DARIs.
 
fairnymph said:
I've only tried bromocriptine & cabergoline, both for depression & to try to treat SSRI induced anorgasmia (so alone & combined with fluoxetine). Both felt very similar & made feel horrible, very dysphoric, plus headache & nausea. I was not impressed, to say the least. I personally seem to only respond well to DA releasers like amphetamine, with little effect from DARIs.
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Were you on antipsychotics when you were taking the dopamine agonists Bromocriptine and Cabergoline?

How did you get these drugs? Were they prescribed by a doctor? If so, what for?

How long did you take the dopamine agonists?

I have ordered Bromocriptine and Pramipexole.
I am hoping that the dopamine agonists will boost my mood and libido, treat anhedonia (lack of pleasure), and brighten my affect etc.Theoretically, these dopamine agonists should treat negative symptoms: blunting of affect, anhedonia, confusing fog of lethargy and indifference, lack of motivation, pre-occupation and initiative, emotional suppression, dampening down of thoughts etc. which - in my case - Abilify is either causing or is failing to treat. Because of Abilify, I no longer derive any euphoria from Marijuanna. I wonder if I'll gain my abilty to derive pleasure from THC when I use Cabergoline or Bromocriptine. THC causes dopamine release in the mesolimbic pathway. Abilify is used precisely to reduce dopaminergic transmission on this pathway. All antipsychotics have the ability to reduce dopamine transmission here. The antipsychotic counteracts and partially nullifies the agonist activity of the dopamine agonists as well as blocks the mesolimbic from overactivating due to THC thereby diminishing the "high".
 
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I self-treated, as I have a strong background in psychiatry & pharmacy. I only took them each twice bc that's how horrible they made me feel. Effects were the same both on & off fluoxetine. I've never taken an antipsychotic; my only mental health problems are OCD & situational depression, & so far based on the mechanisms of the antipsychotics on the market, I don't think any of them would help me or be tolerable. The pills came from a US pharmacy & were definitely legitimate.

I'm not too knowledgeable about weed bc I don't like it or find it medicinal, but I suspect you will not find DA agonists helpful. There's a reason they're so rarely used in psychiatry; they are generally not effective or well tolerated. But I truly hope you prove me wrong! What are you on Abilify for?

I thought I was pretty lucky not to have any side effects from fluoxetine other than the anorgasmia & eventually, after 6yrs on 120mg, a mild EPS hand tremor, which eventually went away after some years.
 
FYI serquel and others are indicated for bipolar depression. Abilify is approved to augment antidepressants (and is an AP).
 
fairnymph said:
I self-treated, as I have a strong background in psychiatry & pharmacy. I only took them each twice bc that's how horrible they made me feel. Effects were the same both on & off fluoxetine. I've never taken an antipsychotic; my only mental health problems are OCD & situational depression, & so far based on the mechanisms of the antipsychotics on the market, I don't think any of them would help me or be tolerable. The pills came from a US pharmacy & were definitely legitimate.

I'm not too knowledgeable about weed bc I don't like it or find it medicinal, but I suspect you will not find DA agonists helpful. There's a reason they're so rarely used in psychiatry; they are generally not effective or well tolerated. But I truly hope you prove me wrong! What are you on Abilify for?

I thought I was pretty lucky not to have any side effects from fluoxetine other than the anorgasmia & eventually, after 6yrs on 120mg, a mild EPS hand tremor, which eventually went away after some years.
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I am taking 400 mg of Abilify per month for the maintenance treatment of positive symptoms of schizoaffective disorder: psychosis (delusions), and mania.
 
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And also there are four dopamingergic tracts in the brain.

The meds used for parkinson's (except selegiline) affect the nigrostriatal tract.

Overall, the cortical tract is populated by D1 receptors, and the limbic tract by D2 receptors. Classic stimulants reach both, but as far as I know the way of sole cortical dopaminergic activity just itself is largely by initial 5-HT2a antagonism, perhaps also due to glutamaterrgic activity from clozapine.
 
fairnymph said:
Is it helping? I assume yes? Are you on any other meds?
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Yes; Abilify is a potent antimanic drug and an effective antipsychotic for me. It definitely works.

I am also on 300 mg of Welbutrin (Buproprion) per day. Bupropion is a Norepinetphrine-Dopamine Reuptake Inhibitor. I use it to combat negative symptoms and depression. Abilify enhances the antidepressant effects of Welbutrin also of SSRI's. I am not depressed nor manic. I am euthymic now. Abilify prevents my mood from elevating too much. I do have anhedonia (lack of pleasure) and lack of motivation, drive, and initiative, which Abilify does not treat by itself, so a dopaminergic antidepressant was added.

I have ordered Bromocriptine and Pramipexole: dopamine agonists. I have done some research and find that I might benefit from a little dopaminergic boost. since I am afraid Abilify must be reducing the activity of my mesolimbic (reward) pathway. That's why I don't feel any reward, pleasure, motivation any longer. I am going to take the dopamine agonists at low doses at first, and then titrate upwards. I am hoping to combat anhedonia, negative symptoms, as well the Abilify-induced sexual dysfunction affecting all phases of sexual function, including loss of libido and diminished orgasm.
 
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fairnymph said:
I've only tried bromocriptine & cabergoline, both for depression & to try to treat SSRI induced anorgasmia (so alone & combined with fluoxetine). Both felt very similar & made feel horrible, very dysphoric, plus headache & nausea. I was not impressed, to say the least. I personally seem to only respond well to DA releasers like amphetamine, with little effect from DARIs.
Click to expand...

Dopamine agonists are very different than releasers / reuptake inhibitors. I don't really have experiences with them, just with memantine which is a NMDA antagonist with additional D2 agonism, said to be equally potent to both targets but it does not share the usual side effects of dopamine agonists, so - it's not a good one to speculate off. Interesting to read about these 4 dopaminergic tracts. Thought that the different behavior of agonists would come from a) dose-dependently hitting auto-receptors so possibly essentially shutting down dopamine release, and b) that with DA it's more about a repetitive firing / release & re-uptake cycle that makes the stimulation and agonists which bind to the receptors and stick to them for a while give a very different signalling behavior.. also there's tonic vs. phasic DA activity, I know little yet about that.

I'm interested in dopamine agonists for treating my severe anhedonia though. Also have SSRI-induced sexual dysfunction, that even appears to have become permanent, it's not a primary concern but it sucks and makes me fear that also other things might have changed permanently for the worse.

Truthometer - probably you know that Abilify works (among others) as a dopamine partial agonist, meaning that it does not completely block the DA receptors like most antipsychotics do but nevertheless it activates them to a much lesser degree than dopamine or a full agonist would do. So by adding a dopamine agonist to it, you more or less put these in rivalery and -might- end up with a manic episode. Although it's quite possible that you benefit from some of its other activities like 5-HT2A antagonism and indeed get just side effects from the dopamine part.
 
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dopamimetic said:
Dopamine agonists are very different than releasers / reuptake inhibitors. I don't really have experiences with them, just with memantine which is a NMDA antagonist with additional D2 agonism, said to be equally potent to both targets but it does not share the usual side effects of dopamine agonists, so - it's not a good one to speculate off. Interesting to read about these 4 dopaminergic tracts. Thought that the different behavior of agonists would come from a) dose-dependently hitting auto-receptors so possibly essentially shutting down dopamine release, and b) that with DA it's more about a repetitive firing / release & re-uptake cycle that makes the stimulation and agonists which bind to the receptors and stick to them for a while give a very different signalling behavior.. also there's tonic vs. phasic DA activity, I know little yet about that.

I'm interested in dopamine agonists for treating my severe anhedonia though. Also have SSRI-induced sexual dysfunction, that even appears to have become permanent, it's not a primary concern but it sucks and makes me fear that also other things might have changed permanently for the worse.

Truthometer - probably you know that Abilify works (among others) as a dopamine partial agonist, meaning that it does not completely block the DA receptors like most antipsychotics do but nevertheless it activates them to a much lesser degree than dopamine or a full agonist would do. So by adding a dopamine agonist to it, you more or less put these in rivalery and -might- end up with a manic episode. Although it's quite possible that you benefit from some of its other activities like 5-HT2A antagonism and indeed get just side effects from the dopamine part.
Click to expand...

Very different indeed. I've considered trying memantine but am a bit wary - it was new back when I first became interested, too. How do you like it? What positive & negative effects do you get?

How long have you been off your SSRI, which one were you on, at what dose & for how long? I'm surprised you're still experiencing anorgasmia bc I returned to normal after a few days of stopping fluoxetine, & sooner for other SSRIs & SNRIs (I've tried most & they all cause complete anorgasmia for me). Hopefully you will eventually heal, as with my tremor. I'm not sure exactly how long that took bc it was so gradual I didn't notice until it was completely gone, which was probably around 8-10yrs ago - so it may have taken as long as 3-5yrs.

I agree there is theoretical potential for mania but I suspect that won't be an issue. Very curious to hear how the OP reacts.
 
Memantine is a weird drug to me. I took it for quite a while, first time was years ago when I was doing low-dosed dissociatives (MXE back then) with increasing frequency and began to get mood swings when they were wearing off, the memantine did level this out pretty well. Also I thought it would help with impulse control and/or against repetitive thoughts and anxiety attacks. Then I moved to my then girlfriend who did not appreciate drug use so I settled for just the memantine, 40mg/d were too much of mind clouding so I did 30mg/d. Initially it also had a somewhat stimulating nature (probably the DA agonism?). Can't tell whether it made me compulsive like other DA agonists can do, but it might be possible because I would eventually slip into destructive drug use again, hiding it from gf and interfering with my life, something I did not have before in this extent, but I'm absolutely not sure.

In retrospective I'd say the dosage might have been too high, I thought that when memantine is intended for the elderly and obviously should not exhibit dissociative-esque side effects then the recommended 20mg/d would be on the lower end of dosage window but it could well have been better to use that or even 15mg/d as it also has a very long half life and does accumulate over time. Well, it's impossible to differentiate between medication related impingement and real life based ones but the positive effects of "real" dissociatives like the pronounced and sustained antidepressive and anxiolytic activity, the support against my introversion etc. faded away with using just the memantine and as said, I began to crave and use other drugs again but in the hiding and less controlled than before.

Eventually I got to a psych clinic where the docs did not know or care about the memantine and discontinued it cold turkey after maybe a year of continuous use. I have also been using clonidine in parallel as a sleep aid, might well have contributed to depression worsening and other side effects, but back then I was obsessed with norepinephrine being bad and responsible for my anxiety.. yeah, so the docs discontinued both and I became pretty agitated and probably mania-like for some time..

Really odd thing is that memantine does not mix well with other NMDA antagonists, while all the others tend not to bite each other. The nicotinic antagonism and thus the muscle relaxation (memantine has been sold as a muscle relaxant before it got re-approved for Alzheimer's) can be pretty strong with higher dosages, I truly wonder how people can do 50mg+ or even 100mg+ like in some of the scattered trip reports. This intense muscle relaxation, and after some time a pretty quick reversal thereof, brought up some anxiety when I did not expect it.

All over I am truly unsure about this med. I had bigger hopes for it, yet it does something and some report to have great success with it. Also it probably helped quite much with cutting down on morphine, and maybe for leveling out emotional impulses.. On the other hand, I fear of suffering from long term dopamine agonist PAWS now as well as it might have added to my sky-high dissociative tolerance with unknown implications. After all, it's been on the market for a long time so the pre-market studies weren't as tight as they are today and as medicinally it's given to the elderly, for a disease that will require staying on it, then who cares about long-term after effects?

It's got some antipsychotic activity at least for me though, and I'd choose it any time over any classical D2 antagonistic antipsychotic.

How long have you been off your SSRI, which one were you on, at what dose & for how long? I'm surprised you're still experiencing anorgasmia bc I returned to normal after a few days of stopping fluoxetine, & sooner for other SSRIs & SNRIs
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I've probably lived a bigger part of my adult life with an SNRI than without, most of it being venlafaxine but well I've used and abused much to many drugs over time to really tell what effects belong to what substance. Just that in the very first weeks of SS/NRI treatment back when I was 17, penis sensitivity, endurance and orgasm intensity changed drastically to the worse. With paroxetine I was completely anorgasmic, when off SSRI I would eventually develop premature ejaculation and with venlafaxine this settled again to something below average but acceptable. Then I had a breakup with my ex, longer period without sex and intense drug abuse, went on buprenorphine and later morphine - on these I usually couldn't even get an erection or then no orgasm and the latter remained even now when I am off the morphine again. This sucks, as I have barely crossed the 30's yet and unfortunately against some hopes it's primarily the physical ability, and part of the hornyness that disappeared but not at all the desire for intimacy. Which would have been a relief, to quit the dependency on the opposite sex for having basic human longings satisfied, with me being one of these guys girls just see as the nice buddy to talk with about the real guys.. what sucks even more and brings me back to drug use, worsening the initial problem.
 
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Very helpful, thanks! I will definitely try some memantine - in fact I'll ask my dr for it tomorrow. The potential muscle relaxation alone is very appealing (the cause of my severe chronic pain is muscle tension/spasticity), & maybe I'll get some good DA effects to help with my fatigue, depression & motivation, & ofc, it could help lower my opiate tolerance.

Wow that REALLY sucks. Are you on anything right now? All your sexual responses/side effects are very common, just what I'd expect. I can't come at all on opiates either, but at least when in WD I get a little fun.

I'm sorry about your relationship issues...I used to want my husband to be sober & he just was an addict behind my back, & I couldn't help him when he ODed. It doesn't work to try to change men.
 
amphetamine is way more than a releaser. It requires some level biopsychology to fully understand. It's main mechanism is called "facillitated exchange disffusion", or, "reverse transport". As a catecholamine, it has affinity for DAT/NET because it tricks the brain into thinking it's DA/NE. It somewhat blocks re-uptake in this manner. Some of it in the presynaptic cell then proceeds to be an MAOI (A). Most that reaches the presnyaptic cell is then transported by VMAT2 into vesicles. in the presynaptic cell This expansion in vesicular neurtoranimstters pushes out natural catacholamines and amphetamine alike into the synapse, which then bind to their given receptors.

Amp is a DA/NE agonist, as well as a TAAR agonist. Trace amines are mostly sympathomimetic like phenylethylamine. But tryptamine is an indolamine (like serotonin).


These manners of catecholiminergic activity synergize.


At higher doses it can collapse the vesicular PH gradient into so monoamines leak into the cytoplasm for release.
 
It was shorthand (can you think of a better way to summarise its effects in such a context?), but yes, you are right. I didn't know that bit at higher doses - how high are we talking?
 
Basically it acts like the monoamines (to a very small extent serotonin), which increases aggregate levels.

I am not sure of the dosage. I just read it in a recent study. But it's high, as is the dose needed to produce an actual antidepressant effect (MAO inhibition).

But side effects can be terrible at an antidepressant dose, not to mention otherwise being neurotoxic. In this realm we're talking 100's of mg's.
 
fairnymph said:
.I used to want my husband to be sober & he just was an addict behind my back, & I couldn't help him when he ODed. It doesn't work to try to change men.
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Really sorry to read that too :( relationships can be complicated matter but yeah agreed, it doesn't work to change people against their will or beliefs. My ex was a pretty heavy party drug and booze user before we got to know each other but my predecessor had a destroying IV opioid habit that broke something within her and well drugs became a red flag, even more so when I got into some legal issues from the breakdown of the RC scene.. unfortunately I have been and am caught in a spiral of emotional problems, self medication, repercussions (legal, social, financial), and so on..

Are you on anything right now? All your sexual responses/side effects are very common, just what I'd expect. I can't come at all on opiates either, but at least when in WD I get a little fun.
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Strangely, after the initial worsening as a teen, I used to be fine with venlafaxine 150mg/d, also helped me to control / delay orgasm somewhat even though an overall blunting happened but yeah as I've said, with the opioids things changed seemingly permanent. Maybe my periodically heavy dissociative abuse contributed its own part, yet I did them (DXM, MXE) before and always got back to baseline as soon as the drugs weared off.

Noticed that with the buprenorphine I had some weird problems to pee at first, thought it'd be usual anticholinergic side effects though even it's apparently uncommon for this substance.

So, at the moment I am back on venlafaxine 75mg/d and occasional DXM / MXE as boosters but I have been off any serotonergic medication for several weeks in the end of 2018 w/o changes. Maybe my body would need longer to readjust its hormones after quitting morphine? I cut down too fast, with the help of DXM I did not really suffer withdrawal, but then sobriety hit me again and I did not stand this for longer than maybe 7 days.. then continued with a tiny 60mg of morphine and other stuff..

Know it's impossible to say anything for sure with such a diffuse consumption regimen. Bit it's frightening that I never had such issues with even remote intensity before and all of a sudden it appears to be the new status quo.

--

Wish you good luck with the memantine!

I'd love to try out bromantane, to compare them but apparently it (Ladasten, the eastern label) has been discontinued by the manufactor and RC bromantane was more often fake than real.
 
You've sure had it rough lately. When it rains is ALWAYS fucking pours. If you ever want to talk, let me know. Often there aren't many people one can talk to openly about such situations. Legal stuff can screw you over mentally really badly, in particular. Seen it ruin far too many people. And I feel intelligent, creative types handle it worse than others. Such a goddamn waste. *shakes fist at WoD*

You're still on venlafaxine - that is most likely the problem. Just bc you could function in it sexually when you were younger (& before doing other drugs), doesn't mean that can't change. You're on a higher dose, too, but not quite high enough to benefit from the DA effects that might counteract sexual side effects. It is certainly possible you need longer than several weeks off it, and without taking any opiates. It's possible if you continue taking ONLY the venlafaxine you'll return to how you were on it before. I would definitely avoid combining it with opiates or any other drug with sexual side effect, though.

Have you considered trying a MAOI? Are you primarily depressed or anxious?

I'll report back on the memantine for sure. Haven't heard of bromantane but will check it out.
 
I had ordered Pramipexole (Mirapex) and Bromocriptine (Parlodel). I had these delivered to me yesterday. I am using them to treat depression and negative symptoms (lack of motivation/ avolition, anhedonia, blunting of affect) as well as "Neuroleptic Induced Deficit Syndrome" from too much Abilify (~20 mg per day). I am using these to give me a slight dopaminergic boost.

Pramipexole is a D2, D3, and D4 receptor agonist, with the highest intrinsic activity on D2(s) receptors and highest affinity at D3 receptors.
Bromocriptine agonizes D2,D3,D4 (D2-family), as well as D1 and D5 (D1-family). Bromocriptine is also an agonist on 5HT1A receptors.
I am using these drugs to lower my prolactin levels and to reverse antipsychotic-induced sexual dysfunction (loss of libido and anorgasmia).

Bromocriptine agonizes the following monoamine receptors:[19]


  • Dopamine D1 family
    • D1 (Ki=682 nM)
    • D5 (Ki=496 nM)
  • Dopamine D2 family
    • D2 (Ki=2.96 nM)
    • D3 (Ki=5.42 nM)
    • D4 (Ki=328 nM)
  • Serotonin 5-HT
  • Adrenergic α family
  • Adrenergic β family
    • β1 (Ki=589 nM)
    • β2 (Ki=741 nM)
 
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