# mirtazapine and dopamine



## johnny10 (May 6, 2012)

Hello,

is mirtazapine dopamine agonist or antagonist? According to wikipedia dopamine antagonist.

I am asking because I get huge restlessness from mirtazapine so I would like to get rid of it. I think it is a kind of restless leg syndrome, though I am not sure. I want to continue with mirtazapine as it helps me a lot with social anxiety.

My doctor prescribed me a dopamine antagonist (tiapride) and I am afraid that it will make it worse, as it is a dopamine antagonist but restless leg syndrome should be treated with dopamine agonist (mainly ropinirole).

It is possible that mirtazapine caused this restlessness because of antagonizing my dopamine - therefore I think I need rather a dopamine agonist. I am not a professional but this sounds logical to me and I am really afraid about that medication which was prescribed to me. What do you think of it?

Thanks


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## Costy (Nov 23, 2012)

Mirtazapine blocks H1 receptor also histamine receptors, and serotonin receptors 5HT2A, 5HT2C, 5HT3.
Through blocking 5HT2C, more Dopamine and Norephinefrine is released in prefrontal cortex, and because that perhaps do you have this simptoms.
But when you take an Dopamine antagonist, you cand have the surprise to have anhedonia and apathy, but is not sure.


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## depressed77 (Dec 9, 2010)

> is mirtazapine dopamine agonist or antagonist? According to wikipedia dopamine antagonist.


Where on wikipedia did you read this?

How long have you been taking mirtazapine and on what dosage?

/depressed77


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## basuraeuropea (Jul 25, 2012)

i mean, it has really weak affinities for d1, d2, d3 and d4 receptor sites as an inverse agonist/antagonist, but it seems to exert its effects on dopamine via its 5ht1a receptor affinity more than the primary mechanism of action. one would need to take quite a lot of mirtazapine for it to touch dopamine receptors effectively with the primary pharmacological action responsible.

that said, it also has a pretty significant affinity for 5ht2c and that purportedly inhibits the release of dopamine which may be the mechanism that's causing the akathisia.

http://www.ncbi.nlm.nih.gov/pubmed/15145142

*Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.*



> *Abstract*
> Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function.


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## johnny10 (May 6, 2012)

Thanks guys. So it is akathisia rather than restless leg syndrome, yep?

My current medications are:
- venlafaxine (75 mg)
- mirtazapine (3,75 mg) (I think this causes the restlessness but on the other hand helps me immensely with SAD)
- bromazepam - I take this now quite a lot, at most 9 mg a day, but I take it only because of this restlessness I feel, because it is huge.

I am thinking about switching mirtazapine to mianserin, maybe it will not cause this side effect but still give me the good effects for SAD (I cannot get the proper data about mianserin as it is quite old).

So what is the bottom line about this drug tiapride (dopamine antagonist)? As I understood from your replies mirtazapine can indirectly increase my dopamine levels and that can be the reason for restlessness, so it looks dopamine antagonist could help me. I mean I would like to stay on either mirtazapine or mianserin because of the positive effects, but somehow I need to counter the side effects of restlessness. So you think I should rather antagonize the dopamine?


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## basuraeuropea (Jul 25, 2012)

tiapride *might* make things worse if the problem is dopaminergic in nature, although it depends on the concentrations and/or transmission rates of dopamine within certain regions of the brain, e.g. the striatum or the nucleus accumbems vs. the substantia ***** or the basal ganglia. it's an odd drug use for the treatment of certain movement disorders but with the possibility of causing eps. hah.

and it is likely akathisia if the problem started when you began taking mirtazapine. it would be quite coincidental if you developed restless leg syndrome and the onset of symptoms coincided with starting mirtazapine.


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## johnny10 (May 6, 2012)

Yes, it started with mirtazapine. That is almost sure. I was taking also amisulpride for quite a long time but then I withdrawn it (actually around that time started this restlessness, but it can be coincidence).

I will rather not take this tiapride, as I am afraid of worsening syndroms of akathisia. Actually antipsychotics can cause akathisia so also therefore my concern.

From what I read propinirole (beta blocker) can help with akathisia. My pdoc does not communicate with me that much and prescribes whatever she wants, so I think I will change her. But it will take time so I want to resolve it somehow now, so I will make an appointment with neurologist. Until that time I hope bromazepam will help me, but I do not want to become addicted on benzos.

My pdoc promised to prescribe me mianserin as I asked her several times (telling her that mirtazapine helped me the most). I hope it will not cause this restlessness, but at least I will try. It is difficult to find out what exactly is the imbalance in my brain chemicals, but with mirtazpaine I was close to balancing it. I am much restrained with doing my CBT when I have this akathisia.


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## basuraeuropea (Jul 25, 2012)

johnny10 said:


> From what I read propinirole (beta blocker) can help with akathisia. My pdoc does not communicate with me that much and prescribes whatever she wants, so I think I will change her. But it will take time so I want to resolve it somehow now, so I will make an appointment with neurologist. Until that time I hope bromazepam will help me, but I do not want to become addicted on benzos.


propranolol, along with a number of other beta blockers can, indeed, help ameliorate akathisia and eps in general.



johnny10 said:


> My pdoc promised to prescribe me mianserin as I asked her several times (telling her that mirtazapine helped me the most). I hope it will not cause this restlessness, but at least I will try. It is difficult to find out what exactly is the imbalance in my brain chemicals, but with mirtazpaine I was close to balancing it. I am much restrained with doing my CBT when I have this akathisia.


mianserin and mirtazapine are extremely similar - exceedingly so.


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## johnny10 (May 6, 2012)

Thanks basuraeuropea for replies. Helped me a lot.


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## basuraeuropea (Jul 25, 2012)

no problem


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## johnny10 (May 6, 2012)

I just found out that in my country propranolol in not distributed. So also other beta blockers can help me? Should it be a nonselective agent like propranolol?


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## basuraeuropea (Jul 25, 2012)

yeah, there are a number of them. but rather than using drugs to combat the side effects of other drugs, you should try to switch to an agent that isn't going to cause, say, akathisia. i think using drugs to minimise the side effects of other drugs is a worthwhile option to explore if you're at the end of your rope, having nothing else to trial, or the drug's benefits far outweigh the detriments for you. i mean, you could be in one or both of these situations, although likely not, and keep in mind that taking a beta blocker daily may come with undesirable side effects of its own.


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## johnny10 (May 6, 2012)

Thanks. That's why I would like to switch from mirtazapine to mianserin, maybe it will not cause this akathisia side effect. But nobody knows.


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## basuraeuropea (Jul 25, 2012)

johnny10 said:


> Thanks. That's why I would like to switch from mirtazapine to mianserin, maybe it will not cause this akathisia side effect. But nobody knows.


maybe, but i wouldn't count on it affecting you all too differently than mirtazapine given their respective pharmacological profiles.


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## johnny10 (May 6, 2012)

basuraeuropea said:


> i mean, it has really weak affinities for d1, d2, d3 and d4 receptor sites as an inverse agonist/antagonist, but it seems to exert its effects on dopamine via its 5ht1a receptor affinity more than the primary mechanism of action. one would need to take quite a lot of mirtazapine for it to touch dopamine receptors effectively with the primary pharmacological action responsible.
> 
> that said, it also has a pretty significant affinity for 5ht2c and that purportedly inhibits the release of dopamine which may be the mechanism that's causing the akathisia.
> 
> ...


I got akathisia both from mirtazapine and trazodone. They both work on 5HT1A receptor. From what I found mianserin does not influence 5HT1A receptor. So is it possible that I will not get akithisia from that? I am just gonna try mianserin.


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## basuraeuropea (Jul 25, 2012)

johnny10 said:


> I got akathisia both from mirtazapine and trazodone. They both work on 5HT1A receptor. From what I found mianserin does not influence 5HT1A receptor. So is it possible that I will not get akithisia from that? I am just gonna try mianserin.


try mianserin. your hypothesis is a decent one. that said, trazodone and buspirone both gave me akathisia while mirtazapine didn't, which is curious as mirtazapine binds more tightly to 5ht1a receptor sites than trazodone. buspirone is another story as a partial agonist, although it has the greatest affinity for the particular receptor site in question out of the bunch.


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## johnny10 (May 6, 2012)

I used buspirone for several years (30 mg a day) but didnt get akathisia from that. From mirtazapine it started slowly to develop (just one hour after taking it), then I stopped mirtazapine and it stopped as well. But after month I started again and developed huge akathisia. When I withdrawn it decreased, but then I started trazodone and it came back. I withdrawn also trazodone but it didnt go to normal even after withdrawal, which I dont inderstand. Probably I would need beta-blockers for a while.

Btw. do you study pharmacology or smth?


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## basuraeuropea (Jul 25, 2012)

johnny10 said:


> I used buspirone for several years (30 mg a day) but didnt get akathisia from that. From mirtazapine it started slowly to develop (just one hour after taking it), then I stopped mirtazapine and it stopped as well. But after month I started again and developed huge akathisia. When I withdrawn it decreased, but then I started trazodone and it came back. I withdrawn also trazodone but it didnt go to normal even after withdrawal, which I dont inderstand. Probably I would need beta-blockers for a while.
> 
> Btw. do you study pharmacology or smth?


my undergrad and grad degrees are in related fields.


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## johnny10 (May 6, 2012)

So I changed my pdoc and she looks good. She is not offended if I talk and ask about medications.

I withdrawn mirtazapine and started mianserin. For akathisia she prescribed me clonazepam and when I asked about propranol she said it is not used now very often but she will consult it with her colleagues.

Hope mianserin will not give me akathisia and clonazepam will cure me from akathsia.


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## Konami (Jul 5, 2011)

basuraeuropea said:


> my undergrad and grad degrees are in related fields.


Related fields?


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## basuraeuropea (Jul 25, 2012)

konamitech said:


> Related fields?


b.sc. in neuropsychology and m.sc.ed in child psychology


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