# Has anyone tried a dopamine agonist?



## Diya (Aug 28, 2008)

.


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## Jrock (Dec 16, 2008)

I have wondered the same thing.


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## jjyiss (May 6, 2006)

does aniracetam count? 

""This shows that aniracetam's anxiolytic mechanism is facilitated by D2/D3 dopamine, nicotinic acetylcholine, and 5-HT2A receptors""

if so then, it lasts 4-5 hours for me, and it works wonderfully at 500mg.


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## miko (Jul 5, 2009)

Hey guys! I'm tried Ropinirole ( because it's cheaper... ), and... wow, it's great, you know, I tried SSRI ( not tolerate it! ), tricylic, mianserin, and many other antidepressants, and I must say that combo of wellbutrin (150 mg), ropinirole and oxybutynin (anticholinergic drug, that slows my heart, stop sweating and make me more calm..., not sure how it's working, but I think it's because M3 acetylcholine antagonism), it's the best social anxiety combo for me !!! Sorry for my english, i'm from Poland  but I want to share it with you. Maybe someone can use it  Pozdro from Poland


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## euphoria (Jan 21, 2009)

miko said:


> Hey guys! I'm tried Ropinirole ( because it's cheaper... ), and... wow, it's great, you know, I tried SSRI ( not tolerate it! ), tricylic, mianserin, and many other antidepressants, and I must say that combo of wellbutrin (150 mg), ropinirole and oxybutynin (anticholinergic drug, that slows my heart, stop sweating and make me more calm..., not sure how it's working, but I think it's because M3 acetylcholine antagonism), it's the best social anxiety combo for me !!! Sorry for my english, i'm from Poland  but I want to share it with you. Maybe someone can use it  Pozdro from Poland


Just take carvedilol or clonidine if you want to lower effects of adrenaline/noradrenaline (anxiety, fast heartbeat, etc.). Benzos would also help this, and so would magnesium glycinate. SSRIs would reduce anxiety if you titrate your dose up very slowly so it is tolerable, and they could be taken with mirtazapine for less side-effects and better response.

Oxybutynin taken with Wellbutrin and ropinirole is just a recipe for psychosis (particularly of the paranoid type) due to oxybutynin blocking cholinergic receptors in the brain. Taking these drugs together will make you crazy and stupid, it's just a matter of time.


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## miko (Jul 5, 2009)

Clonidine make me feel like **** :| beta adrenolitics is good, but for me (I have something like Raynaud's symptome), they make me cold. Carvedilol is also alfa blocker, but I prefer Nebivolol+Alfa Blocker. Benzos is also good but I don't want to take it. Believe me, even Benzos don't make me feel soo good as dopamine agonists! I don't know how to explain this in english, but this meds take back my laught, my humour, make me calm. I don't know, but maybe I have restless legs because this meds make me so patient. I never know that I can be so patient!!! 

I know that anticholinergics are bad. They can take you memory. There is study that say Oxybutynin decrease memory, and I want change it to glycopyrrolate (avert),that don't cross blood/brain barrier.

SSRI make me Akathisia, Restless Legs, and Anxiety I have never been :f That's I search net for other meds that make me cure from social anxiety. And I found it. For me it's easy choice -anxiety or danger with my meds. You know what I've chosen...

I have no schizo episodes, so maybe I'm in this good situation that I can take meds working on dopamine. In my life, Parkinsons disease is more possible


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## Beffrey28 (Jan 15, 2009)

miko said:


> I know that anticholinergics are bad. They can take you memory. There is study that say Oxybutynin decrease memory, and I want change it to glycopyrrolate (avert),that don't cross blood/brain barrier.


Won't nootropics and supps like Piracetam, Choline, Huperzine A and Acetyl L-Carnitine help against the cognitive decline?


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## miko (Jul 5, 2009)

Don't know, but anticholinergics block acetylcholine receptors, and Choline, ACL increase acetylcholine levels. Maybe Nootropics may help if they working on other rules, like piracetam? Oxybutynin is bad becauce it's blocking three M receptors, but it's cheap and available ( Ditropan ). Tricylic blocking mainly M1 receptors in brain, that's they can do excessive sweating, and all M3 blocking Oxybutynin is used in excessive sweating treatment. In Parkinsons, there is no dopamine, and too much acetylcholine, and that's why we have excessive sweating, seborrhea, drooling. M3 acetylcholine receptors respond for glands secretion. There is study on net that's say too much acetylcholine is one of the reasons of depression. Anticholinergics working on me, increase my mood, I think it's because, they somehow increase dopamine.


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## Beffrey28 (Jan 15, 2009)

miko said:


> Don't know, but anticholinergics block acetylcholine receptors, and Choline, ACL increase acetylcholine levels. Maybe Nootropics may help if they working on other rules, like piracetam? Oxybutynin is bad becauce it's blocking three M receptors, but it's cheap and available ( Ditropan ). Tricylic blocking mainly M1 receptors in brain, that's they can do excessive sweating, and all M3 blocking Oxybutynin is used in excessive sweating treatment. In Parkinsons, there is no dopamine, and too much acetylcholine, and that's why we have excessive sweating, seborrhea, drooling. M3 acetylcholine receptors respond for glands secretion. There is study on net that's say too much acetylcholine is one of the reasons of depression. Anticholinergics working on me, increase my mood, I think it's because, they somehow increase dopamine.


Ok thanks for the info. Reason i ask is because i want to try Oxy for facial blushing. On some blushingforums they say it helps a lot. 
But my memory is pretty strong and i really don't want to mess a lot with my shortterm memory. I have Piracetam, Choline and ALCAR at home.
Maybe one of the Med experts can explain if supps and nootropics help when taking Oxybutynin?


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## miko (Jul 5, 2009)

Facial blushing? So you are getting red in some situtations? Hmm, oxy stops sweating, so you can get red from getting up your temperature  You know, I'm always white as a sheet  I want to be red, but my blood cyrculation is bad. If you want to try Oxy, better is Avert! http://www.pharmacy.ca/cgi-bin/Phar...ntiperspirant&ORDER_ID=!ORDERID!&GETSPECIALS= you can buy it here


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## Beffrey28 (Jan 15, 2009)

miko said:


> Facial blushing? So you are getting red in some situtations? Hmm, oxy stops sweating, so you can get red from getting up your temperature  You know, I'm always white as a sheet  I want to be red, but my blood cyrculation is bad. If you want to try Oxy, better is Avert! http://www.pharmacy.ca/cgi-bin/Phar...ntiperspirant&ORDER_ID=!ORDERID!&GETSPECIALS= you can buy it here


Yes my head turns bright red in the most 'normal' situations like somebody asking a question. The problem is not the blushing, but the fear of it. 
I've always blushed, but only since my 19th i developed a phobia for it.
That phobia turned into a social phobia. Before i had no trouble in social situations, because the blushing wasn't a big issue.
It became a huge issue after someone commented about it in a very harsh way. I started avoiding things and it got worse and worse, eventually becoming a social phobia.
If i can find something that prevents me from getting red, i know i can turn the SA around.
I've read the Oxy works very well for a lot of blushers. Only problem is the side effects. But if they are not too bad i will trade my blushing for it anyday.
Maybe the memory problems with Oxy will turn out positive. Maybe they will make me forget about blushing episodes from the past lol.
Thanks for the info!


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## Beggiatoa (Dec 25, 2004)

Pramipexole is great stuff and probably deserves its own thread. Best dopaminergic I've come across.


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## Jrock (Dec 16, 2008)

How is a Dopamine Agonist suppose to improve SA?


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## miko (Jul 5, 2009)

Yeah, dopamine agonists it's best med for social anxiety, for me


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## euphoria (Jan 21, 2009)

Dopamine agonists are probably effective for SA, but I'd much prefer to hit all the dopamine receptors with a combination of selegiline and another dopaminergic (low dose). Targeting individual receptors (e.g. D3 with pramipexole) sounds like it'd be give unbalanced effects and not the full benefits of something like amphetamine.

Dopamine, serotonin, norepinephrine and acetylcholine all have peripheral effects too, so I would be very wary of making up random cocktails of individual receptor agonists, since agonism on all receptors (such as with releasing agents) is a lot more studied. For example, the serotonin 2B receptor subtype is known to cause severe heart valve problems.

I'm a hypocrite for saying that, but it needed to be said.


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## miko (Jul 5, 2009)

But pramipexole and ropinirole don't have agonism to 2b receptor. The only known danger for d3 receptor is gamling, compulsive sex and eating too much.

And agonism of d2 receptor can make psychosis.

I'd like to know is it possible that SSRI can make hear problems. SSRI hit 5-HT2 receptors, and meds that hit this receptors can make heart disease ( like euphoria said ). There is cancer that make too much serotonin.


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## miko (Jul 5, 2009)

Yes I know, I only write that because old dopamine agonists hit 5-ht2b receptor and have heart disease risk.


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## Medline (Sep 23, 2008)

rocknroll714 said:


> As for euphoria mentioning 5-HT2B, obviously he didn't mean that dopamine receptor agonists hit it.





miko said:


> Yes I know, I only write that because old dopamine agonists hit 5-ht2b receptor and have heart disease risk.


Cabergoline and Pergolide...


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## euphoria (Jan 21, 2009)

rocknroll714 said:


> Not to mention nausea from D2/D3 receptor agonists. You'd need a reeeally high dose of a dopamine receptor agonist to cause psychosis by the way. D4 is also implicated, but apparently not D3. Personally, I'm not even sure if it'd be possible to take a dose high enough to cause psychosis on account of most dopamine receptor agonists' very long half-lives (which would make them last for days and make it impossible to sleep if such a dose were taken; hence, they're relatively non-addictive in nature) and tendency to induce severe nausea with such doses.


If a drug is pleasurable enough, people have no trouble taking it for days on end (c.f. meth addicts).



> As for euphoria mentioning 5-HT2B, obviously he didn't mean that dopamine receptor agonists hit it. He was just making a point. Also, notably, the SSRIs have a very low risk of causing heart disease. In fact, no one has ever been reported to have developed cardiac fibrosis due to taking any SSRI or other antidepressant for that matter, with the notable exception of newborns in pregnant mothers taking such drugs. On the other hand, SSRIs have been associated with a significantly increased risk of heart disease in later life in people taking them for very long perioids of time.


Looks like we'll need to find a 2B antagonist then.


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## miko (Jul 5, 2009)

Mianserin/Mitrazapine.


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## euphoria (Jan 21, 2009)

As far as I'm aware, they block 2A and 2C, but not 2B.


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## miko (Jul 5, 2009)

IUPHAR receptor database -> http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2322

mianserin Antagonist 7.3 
mianserin Antagonist 8.8-7.9


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## euphoria (Jan 21, 2009)

On that basis, MAOIs could be even worse than SSRIs for heart valve damage, due to their elevation of tryptamine levels.

Am I right in assuming mirtazapine should share 2B blockade due to its close similarity to mianserin? Also, is 2B anxiolytic or anxiogenic, depressive or antidepressive?

I am sooo looking forward to getting more mirtazapine.


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## euphoria (Jan 21, 2009)

Medline said:


> Since when do SSRI cause heart valve damage? I also never heard that MAOIs cause that.


I meant heart disease, rocknroll said above that SSRIs increase risk of it.


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## Medline (Sep 23, 2008)

The relationship between depression and heart disease is very complex. In the following large study of patients with clinical heart failure (62% with ischemic disease) just depression but not treatment with SSRIs was associated with an ~ 30% increased mortality risk:



> *Antidepressant use, depression, and survival in patients with heart failure.*
> 
> *O'Connor CM*, *Jiang W*, *Kuchibhatla M*, *Mehta RH*, *Clary GL*, *Cuffe MS*, *Christopher EJ*, *Alexander JD*, *Califf RM*, *Krishnan RR*.
> 
> ...


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## euphoria (Jan 21, 2009)

rocknroll714 said:


> The 5-HT2B receptor is anxiolytic and antidepressant by the way. Notably, I recently found out that although the 5-HT3 receptor is [somewhat] anxiogenic, it's paradoxically antidepressant at the same time. This makes sense as 5-HT3 receptor antagonists inhibit the reinforcing effects of opioids, alcohol, and stimulants; or, basically in concept, those of any pleasurable substance. This explains why mirtazapine can make people somewhat apathetic and overly calm or mellow, as well as why it made me feel like all my dopamine was drained upon taking it with phenelzine (Nardil) (though, not in necessarily in a significantly anxiogenic or depressive way, just sort of in an apathetic way). Which, in other words, is really gay. Lower doses than 45 mg (which is what I took) such as 15-30 mg may be somewhat more suitable..


Hmm, yeah. When I withdrew from mirtazapine, I felt nauseous and depressed, but simultaneously like I'd emotionally re-awoken. Was kind of cool, in a depressing, I-hate-feeling-like-this way.


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## RockiNToM (Jun 15, 2009)

I hear Buspar/Buspirone has some weak dopamine agonist properties, but I'm not sure at what dose. It also seems to work better in conjunction with anti-depressants rather than on its own. 

From personal experience, Buspar does do something, but I'm not sure what actual benefit it gives. On a low dose of 5mg when I was taking it with an SSRI it made me quite sleepy as weird as that may sound and I think to some degree helped with my anxiety. I discontinued it because I kept getting constipation when I took it. 

Obviously it doesn't work as good as many other medications, but I think it would be interesting to know how it works and what it does.


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## euphoria (Jan 21, 2009)

Isn't buspirone a weak D2 antagonist?


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## RockiNToM (Jun 15, 2009)

No idea, but it does something with dopamine. That's all I've heard.


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## honastud (Jul 13, 2009)

whats the verdict? ^ I'm ready to toss a couple of these back?


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## miko (Jul 5, 2009)

Yeah, Buspar is weak D2 antagonist. For me, mianserin haven't antidepressant activity, but it's the only med that can help me with ssri-induced akathisia.


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## Edwin (Jun 19, 2008)

Buspar imo, will just give you a dizzy ride through life. But I would agree it lowers anxiety. Sucks for sociability though.


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## euphoria (Jan 21, 2009)

If anyone is taking pramipexole, they should be aware that NMDA antagonists are essential to any dopaminergic regimen, and also that pramipexole will make you feel awful unless you use high doses and/or wait through several weeks of the bad feelings.


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## Edwin (Jun 19, 2008)

I've read up on Pramipexole, but is it due to autoreceptor agonism that you have an initial period of lowered dopamine activity?


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## miko (Jul 5, 2009)

Something about acetylcholine and dopamine:

"We report that M1 deficiency leads to elevated dopaminergic transmission in the striatum and significantly increased locomotor activity. M1-deficient mice also have an increased response to the stimulatory effects of amphetamine. Our results provide direct evidence for regulation of dopaminergic transmission by the M1 receptor and are consistent with the idea that M1 dysfunction could be a contributing factor in psychiatric disorders in which altered dopaminergic transmission has been implicated."

"The Acetylcholinesterase Inhibitor Galantamine Inhibits d-Amphetamine-Induced Psychotic-Like Behavior in Cebus Monkeys"

"Multiple Muscarinic Acetylcholine Receptor Subtypes Modulate Striatal Dopamine Release, as Studied with M1-M5 Muscarinic Receptor Knock-Out Mice"

"Interestingly, in vivo microdialysis studies showed recently that M1 receptor-deficient mice have significantly elevated levels of extracellular dopamine in the striatum, probably because of increased dopamine release "

So maybe acetylcholine hyperactivity blocks dopamine release?
And that's why muscarinic receptors blocker Oxybutynin works on my depression...


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## euphoria (Jan 21, 2009)

I know about the dopamine-acetylcholine link, but how can you think blocking acetylcholine is a good method of treating depression? It may make you a bit happier, but also very stupid and forgetful. Why not increase both dopamine and acetylcholine? Then you'll fight depression without potential for psychosis.


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## miko (Jul 5, 2009)

Yes, increase dopamine is good, but acetylcholinesterase make depression ( more acetylcholine = depression ). There is study about that on net.


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## itsamystery (Jul 26, 2009)

Please try a beta blocker (Inderal). Your doctor will easily prescribe it for social anxiety--you can take a small dose every day for your situational phobias--it works all day, doesn't cause addiction, is very inexpensive. It's been a lifesaver for me. Minimal side-effects as the low doses that it takes to prevent blushing, hand tremors, etc which plagued me for years.


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## euphoria (Jan 21, 2009)

miko said:


> Yes, increase dopamine is good, but acetylcholinesterase make depression ( more acetylcholine = depression ). There is study about that on net.


I know, but if you simultaneously boost dopamine, you get better cognition AND less depression. Also, blocking muscarinic acetylcholine receptors causes tachycardia, which probably wouldn't help those with panic attacks.

Why not just take a beta-blocker like suggested? Or even a benzo, seeing as you're willing to sacrifice cognition and memory. Either are better than a crappy anticholinergic, seriously. It's the equivalent of drinking vodka all day to relieve anxiety -- it works, but is a very poor solution compared to the other things out there.


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## crayzyMed (Nov 2, 2006)

Trivastal its on its way for me, its a non sedating dopamine agonist, so i wouldnt have to get trough all those side effects before it works.

Very interesting thread!

Also, shouldnt a low dose sulpiride block the sedation dopamine agonists cause? Because it blocks the autoreceptors that also seem to respond to a dapomine agonist.


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## miko (Jul 5, 2009)

I want to try trivastal (piribedil) too, becouse on ropinrole I have a sleep attacks :f And it's have vasodilation effect. Dopamine agonists works good on my anhedonia.


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## crayzyMed (Nov 2, 2006)

miko said:


> I want to try trivastal (piribedil) too, becouse on ropinrole I have a sleep attacks :f And it's have vasodilation effect. Dopamine agonists works good on my anhedonia.


Heres a list of trivastal experiences, it looks pretty good, studies look promosing too:



> Psychomotor and cognitive effects of piribedil,
> a dopamine agonist, in young healthy volunteers
> by
> Schuck S, Bentue-Ferrer D, Kleinermans D,
> ...





> Great Stuff. 50 mg first thing in the morning.





> Hey everyone,
> 
> It's been a long time since I've posted here. Anyways, has anyone else ever tried Trivastal(piribedil)? I tried it for the first time today. I've noticed better concentration, improvement with information processing, verbal fluency, etc. It's completely different than any other dopamine agonist I've tried. Hopefully, the effects continue. Has anyone had experience with it?





> Yes, I've been using Trivastal (piribedil) for quite some time, and have to say its the best dopaminergic drug out there, without side-effects. Pretty much same effects as yours + libido over the roof ;-)





> Yeah, I've found most dopamine agonists to be somewhat sedating(Mirapex, Bromo, Cabergoline). I don't notice any sedating effect with Trivastal though. I think it's because of the additional noradrenergic properties. I'm interested to hear if other people have a similar experience.





> I tried trivestal briefly, and I HATED it. Both times I tried it I descended into a hopeless depression-like feeling which lasted for the rest of the day. I lied huddled under blankets shivering on my couch, eating take out food with a kind of desperation. To each his own, I have 27 tablets left if anyone (US preferred) wants to take them off my hands for $45 shipping included.





> ok...took it 50mg dose with breakfast before going to work.
> 
> 30-40 minutes later i star getting ranndom erections on the office.
> 
> ...





> 50mg feedback:
> 
> I took it just with my regular vitamins, and a little green tea.
> 
> It feels like C+Y almost, no measurable increase in focus, feel a lot more agitated and "excitotoxic" and worse, I feel no serotonine whatsoever. dissapointed thus far. what is the HL of this compound? this could be becasue I'm exausted mentally today but heck this is why I need this





> I'm 61. I've been retired since '99. At this age, things are wearing out. I was having mild depression with melancholy. I had no dreams. I was sleepy, had no motivation, and lethargic. I was drinking coffee all morning. As we age, we loose mental sharpness and memory skills. I felt like I was mentally dead.
> 
> I began to use 100mg of 5-HTP about one hour before bed. The depression symptoms left within several days. I began dreaming again. I began to sing a little to myself during the day.
> 
> ...





> Well this morning I downed one 50mg pill and so far i have been slightly dissapointed...it's hard to describe what i'm feeling slight energy but also with the occassional yawn but i am noticing when typing this the words come out a little bit better but that could be placebo...who knows
> 
> Would it be bad to throw in 500mgs of DLPA in hope that it'll synergize with it?
> 
> I might post at the end of the day and give a full evaluation of it!


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## miko (Jul 5, 2009)

Yes,yes,yes. Don't compare beta blockers with antimuscarinic agents! Beta blockers doing just a little for my SA - lower heart rate and less sweating. Anticholinergic / antimuscarnic doing something other. It's hard to describe (especially to guy from east-my english is not good :f), but i feel dopamine on this meds - like from no other med - wellbutrin (just a little, and noradrenaline makes me anxious). 

Dopamine agonists it's good too. Many things makes me happy, and I feel pleasure from music, sport and other things. Like in the past...

Oxybutynin is very similar to scopolamine. It's blocks M1,M2,M3, not only M1. And it's cheap 

I'm reading now interesting text above - thanks for it.

"D2-like (D2, D3, and D4) receptors inhibit acetylcholine release, M1, M2, and M5 receptors inhibit dopamine release, and M3 and M4 receptors enhance dopamine release." - very interesting. So thats why block of M1,M2 can release dopamine? And maybe D2 dopamine agonist can block acetylcholine release.

"All we can really go on for now is that general acetylcholine depletion results in antidepressant and anxiolytic effects, general acetylcholine enhancement results in depressive and anxiogenic effects, and certain muscarinic anticholinergics like scopolamine produce antidepressant and anxiolytic effects, while most others do not." -true

That's why tricyclic have antidepressants effect if SSRI don't work. But taking it for a long time... a little scary...


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## Medline (Sep 23, 2008)

miko said:


> "All we can really go on for now is that general acetylcholine depletion results in antidepressant and anxiolytic effects, general acetylcholine enhancement results in depressive and anxiogenic effects, and certain muscarinic anticholinergics like scopolamine produce antidepressant and anxiolytic effects, while most others do not." -true
> 
> That's why tricyclic have antidepressants effect if SSRI don't work. But taking it for a long time... a little scary...


Most TCAs work as NRIs which might be one reason they work when SSRIs don't. I also don't think that general acetylcholine enhancement results in depressive and anxiogenic effects.


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## jim_morrison (Aug 17, 2008)

Not to mention that most TCA's also cause 5HT-2 blockade, which may be another reason why they may work when SSRI's don't.


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## jim_morrison (Aug 17, 2008)

Btw heres the presumptive mechanisms thought to mediate the antidepressant effect of various TCA's;

Amitriptyline - 5-HT reuptake inhibition ++ / NE reuptake inhibition ++ /
5-HT2 antagonism ++

Imipramine - 5-HT reuptake inhibition ++ / NE reuptake inhibition ++ /
5-HT2 antagonism +

Clomipramine - 5-HT reuptake inhibition +++ / NE reuptake inhibition + /
5-HT2 antagonism ++

Nortriptyline - 5-HT reuptake inhibition + / NE reuptake inhibition +++/
5-HT2 antagonism ++

Desipramine - NE reuptake inhibition +++


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## miko (Jul 5, 2009)

For me - Amitryptyline is the best. It have stongest anticholinergic effect. Other 3 cyclics don't work on me.


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## Medline (Sep 23, 2008)

jim_morrison said:


> Btw heres the presumptive mechanisms thought to mediate the antidepressant effect of various TCA's;
> 
> Amitriptyline - 5-HT reuptake inhibition ++ / NE reuptake inhibition ++ /
> 5-HT2 antagonism ++
> ...


Amitriptyline can be combined with MAOIs like tranylcypromine:

http://www.ncbi.nlm.nih.gov/pubmed/8453432
http://www.ncbi.nlm.nih.gov/pubmed/1573032
http://www.ncbi.nlm.nih.gov/pubmed/2071885 
http://www.ncbi.nlm.nih.gov/pubmed/6342565
http://www.ncbi.nlm.nih.gov/pubmed/7435677

but Imipramine is strictly contraindicated because of risk of serotonin syndrome:

http://www.ncbi.nlm.nih.gov/pubmed/12927331
http://www.ncbi.nlm.nih.gov/pubmed/14063404

The German manufacturer of tranylcypromine states that "primary noradrenergic TCAs like Amitriptyline, Doxepin, Trimipramine and Nortriptyline can be combined with tranylcypromine - but Imipramine and Clomipramine can not - because of risk of potential fatal serotonin syndrome". You sure Amitriptyline and Imipramine cause the same degree of 5HT reuptake inhibition? And if they do, I am confused by this.


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## jim_morrison (Aug 17, 2008)

Medline said:


> Amitriptyline can be combined with MAOIs like tranylcypromine:
> 
> http://www.ncbi.nlm.nih.gov/pubmed/8453432
> http://www.ncbi.nlm.nih.gov/pubmed/1573032
> ...


Oops my bad, I guess what I was referring to was the similair NE:5HT ratio balance of Imipramine, and Amitriptyline, 1:2.5 and 1:1.6 respectively, atleast according to Preskorn (Figure 3.3), but I see your point, imipramine is generally regarded as a more potent SERT reuptake inhibitor.

http://www.preskorn.com/books/ssri_s3.html


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## jim_morrison (Aug 17, 2008)

What does sigma-1 receptor agonism do anyway? I've heard that being touted as one of zolofts defining features too.

I agree though, they'd be pretty badass if they were 'clean', heck even take out the muscarinic acetylcholine receptor blockade (If theres one type of psychopharm med on the planet which I would not touch its an anticholinergic!), the ion channel blocking, and the alpha-adrenergic receptor antagonism, but leave in the histamine blockade and I would have settled for them.

Edit; one thing though, from one perspective, cymbalta induces serotonin/norepinephrine reuptake inhibition quite similair to that of the TCA's, yet in that big head-to-head meta analysis of 12 new generation drugs, cymbalta scored quite poorly, any thoughts on why this might be?


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## euphoria (Jan 21, 2009)

miko said:


> Dopamine agonists it's good too. Many things makes me happy, and I feel pleasure from music, sport and other things. Like in the past...


How severe was your anhedonia before trying the dopamine agonists? Currently I get so little pleasure from anything that it's not even worth trying, so I'm going to ask for one to augment sertraline. There isn't much better than serotonin/dopamine synergy for anhedonia . Also, does it work for all "hedonic pursuits" or just some? Thanks.


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## crayzyMed (Nov 2, 2006)

euphoria said:


> How severe was your anhedonia before trying the dopamine agonists? Currently I get so little pleasure from anything that it's not even worth trying, so I'm going to ask for one to augment sertraline. There isn't much better than serotonin/dopamine synergy for anhedonia . Also, does it work for all "hedonic pursuits" or just some? Thanks.


Be carefull to slowly titrate your dose tough, dopamine agonists will make you feel alot worse the first 2 weeks.


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## miko (Jul 5, 2009)

My anhedonia came gradually. Music, sport - anything from the past, haven't meaning for me :f becouse I haven't pleasue from this things.. I don't tolerate any SSRI. Sertraline is SSRI I try 6 months --> big akathisia, sweating, fast heat rate -> benzo :f I hate this drugs! I haven't feel worse in all my life. When I'm taking 5-HT2 antagonists with SSRI akathisia is not so strong, so I think I need dopamine. I try dopamine agonists and it's the best med for me. For this moment I can take - wellbutrin, coaxil, dopamine agonists, selegiline - this things works for me.

I haven't any withdrawal feelings from dopamine agonists. And I "jump" from 0,25 to 0,5 mg ropinirole without any feelings.

Try it for week or two? I think this med it's Underestimated.

Sorry for english.


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## crayzyMed (Nov 2, 2006)

miko said:


> My anhedonia came gradually. Music, sport - anything from the past, haven't meaning for me :f becouse I haven't pleasue from this things.. I don't tolerate any SSRI. Sertraline is SSRI I try 6 months --> big akathisia, sweating, fast heat rate -> benzo :f I hate this drugs! I haven't feel worse in all my life. When I'm taking 5-HT2 antagonists with SSRI akathisia is not so strong, so I think I need dopamine. I try dopamine agonists and it's the best med for me. For this moment I can take - wellbutrin, coaxil, dopamine agonists, selegiline - this things works for me.
> 
> I haven't any withdrawal feelings from dopamine agonists. And I "jump" from 0,25 to 0,5 mg ropinirole without any feelings.
> 
> ...


Thank you for your experience

Very interesting combo, should supercharge dopamine!


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## crayzyMed (Nov 2, 2006)

Opipramol looks interesting:



> Hi Ed,Philipa and everyone :
> 
> Sorry for my slowness!!
> 
> ...





> I am an American living in Germany. I have had GAD, depression, and panic attacks my whole life. I have been on a variety of SSRI's and TCA's. Most recently I was on imipramine and diazapam for my anxiety etc. I could tolerate it but the imipramine still bothered me. My German doctor suggested that I try opipramol. I did a seamless switch from the imipramine. The opipramol started working and I eventually got off diazapam also. So far so good. My question is, does anyone know if opipramol is available in the U.S.? I will probably go back in 2 yrs and am concerned about not being able to find this drug that really works for me. Any help would be greatly appreciated.


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## jim_morrison (Aug 17, 2008)

rocknroll714 said:


> Some binding data on duloxetine from this study:
> 
> 
> 
> ...


Yeah, it's a mystery, perhaps venlafaxine really is incorporating the opioid system afterall 

"Venlafaxine has an analgesic effect that is independent of its antidepressant activity. The results of clinical studies suggest that the opioidergic system has a role in the analgesic effect of venlafaxine. Antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) combined with the alpha2-adrenergic receptor. This opioid profile may be one of the explanations to venlafaxine efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity."

http://www.emedexpert.com/facts/venlafaxine-facts.shtml

...Not sure how much I buy into that though, considering that further down the page it contradictorily states; "Venlafaxine is not a controlled substance. It has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors."


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## jim_morrison (Aug 17, 2008)

Although see here http://www.cnsforum.com/imagebank/item/antidep_uptake_specific/default.aspx
and http://www.preskorn.com/columns/9911.html here, 
and you'll notice that venlafaxines binding profile is much higher for 5HT and NE than claimed by other sources, Perhaps it's metabolite O-desmethylvenlafaxine (ODV) (Which stahl claims is responsible for about 50-70% of the benefit in normal metabolisers) is pulling most of the weight for it. *shrugs*


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## miko (Jul 5, 2009)

Two years ago I have opipramol for 1 year (with doxepine), and it's good for anxiety, but it's not antidepressant (haven't increase mood) - a little sedating... good med.


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## euphoria (Jan 21, 2009)

miko said:


> Two years ago I have opipramol for 1 year (with doxepine), and it's good for anxiety, but it's not antidepressant (haven't increase mood) - a little sedating... good med.


When I chose sertraline as my anxiolytic/antidepressant, part of the reason was its sigma receptor affinity, a property it shares with opipramol (sertraline probably at a substantially milder level though). Also for the weak DRI ability, but really just because sertraline is ranked as one of the best SSRIs for anxiety & depression.


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## jim_morrison (Aug 17, 2008)

euphoria said:


> When I chose sertraline as my anxiolytic/antidepressant, part of the reason was its sigma receptor affinity, a property it shares with opipramol (sertraline probably at a substantially milder level though). Also for the weak DRI ability, but really just because sertraline is ranked as one of the best SSRIs for anxiety & depression.


I wonder how much the DRI affinity actually adds to sertraline, I guess a good measure would be if it causes less sexual dysfunction than the other SSRI's?

The other good thing about zoloft, aswell as lexapro, is that neither have Cytochrome P450 enzyme inhibiting properties (in contrast with most other SSRI's, hence less potential for drug interactions), and also the fact that both have optimal half lifes of approx 25 - 30 hrs, hence not too short nor too long. I believe that both of these factors may contribute to the fact that both drugs often score high with patient acceptability.


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