Has anyone tried a dopamine agonist?

[euphoria]

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.

[miko]

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.

[rocknroll714]

Originally Posted by miko

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.

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.

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.

[miko]

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

[Medline]

Originally Posted by rocknroll714

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

Originally Posted by miko

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

Cabergoline and Pergolide...

[euphoria]

Originally Posted by rocknroll714

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.

[miko]

Mianserin/Mitrazapine.

[euphoria]

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

[miko]

IUPHAR receptor database -> http://www.iuphar-db.org/GPCR/Recept...eceptorID=2322

mianserin Antagonist 7.3
mianserin Antagonist 8.8-7.9

[euphoria]

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.

[rocknroll714]

Originally Posted by miko

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

Originally Posted by Medline

Cabergoline and Pergolide...

Right, so that's what you meant..

[euphoria]

Originally Posted by Medline

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.

[rocknroll714]

Originally Posted by miko

Mianserin/Mitrazapine.

Originally Posted by euphoria

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

Originally Posted by miko

IUPHAR receptor database -> http://www.iuphar-db.org/GPCR/Recept...eceptorID=2322

mianserin Antagonist 7.3
mianserin Antagonist 8.8-7.9

Originally Posted by euphoria

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.

Mianserin and mirtazapine are relatively weak at blocking the 5-HT2B receptor in comparison to the 5-HT2A, 5-HT2C, and 5-HT3 receptors. As an example, mirtazapine has about ~10 nM affinity for 5-HT2A, 5-HT2C, and 5-HT3 receptors, and about ~300 nM affinity for the 5-HT2B receptor; which, would basically be clinically negligible. I'm not sure what mianserin's affinities are, but based on its close chemical similarity to mirtazapine, it should also be pretty weak, if not fully insignificant.

The 5-HT2B receptor is potently anxiolytic comparable to benzodiazepines by the way (according to a few studies I read the other day). 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/seemingly in concept, those of just about any pleasurable substance. This explains why mirtazapine can make people somewhat apathetic and "overly calm/mellow", as well as why it made me feel like "all my dopamine was drained" upon taking both alone and with phenelzine (Nardil) (though, not in necessarily in a significantly anxiogenic or depressive way, just sort of in an apathetic way from my experience). 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, but I think it'd merely be a less potent apathetic effect..

[rocknroll714]

Originally Posted by euphoria

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

See this which I posted elsewhere:

Originally Posted by rocknroll714

Your doctor is a ****ing incompetent moron!!

It sounds to me exactly like pulmonary hypertension. I highly doubt it has anything to do with your anxiety at all. I mean you discontinued the citalopram (Celexa) and the effect completely subsided. I think the cause is quite obvious if I do say so myself.

Through excessive activation of the serotonin 5-HT2B receptors, the selective serotonin reuptake inhibitors (SSRIs) and related antidepressants may sometimes significantly increase blood pressure in the pulmonary artery of the heart, putting heavy strain on it as a result, thereby causing pulmonary hypertension, and may potentially even cause the often fatal cardiac fibrosis; hence, at least regarding the former, the chest pain you're experiencing. It should be noted, however, that the risk of full-blown cardiac fibrosis is considered to be substantially low, and no one has even known to have fully developed it as a result of taking an SSRI, with the notable exception of newborns in pregnant mothers taking them that is. Nonetheless, the risk is still indeed present, especially that of pulmonary hypertension; which, on the other hand, has been reported numerous times.

The anorectic agent fenfluramine (Pondimin, Fen-Phen), which is a selective serotonin releasing agent (SSRA), as well as potent 5-HT2B receptor agonist, was withdrawn from the market in 1997 because it caused numerous heart failures and killed a bunch of people, as well as required many heart transplants in those that managed to survive, on account of the effect.

Other drugs and supplements which have been prominently associated with the adverse side effect include aminorex (Menocil) and chlorphentermine (Apsedon, Desopimon, Lucofen) (both of which have been widely discontinued as a result), anything that acts as a potent and direct serotonin 5-HT2B receptor agonist (such as methysergide (Sansert) and pergolide (Permax)), and 5-HTP, as well as the illicit street drugs MDMA (Ecstasy; E, X, XTC) and its chemical relatives, and 4-methylaminorex (4-MAR, 4-MAX; Ice, EU4EUH (or Euphoria)). The SSRIs, selective-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), other serotonin reuptake inhibitors (SRIs) like sibutramine (Meridia, Reductil), and MAOIs, as well as L-tryptophan and pretty much anything that else that can significantly elevate general serotonin levels, may all cause it to a somewhat less common extent.

Don't worry though, it's fine if you get it acutely or for only a short period of time (i.e., a few weeks to months), but when you take an antidepressant or another kind of drug or supplement that significantly elevates serotonin levels chronically for a very long period of time (i.e., years) with the effect present, it can be extremely dangerous.

You're not alone by the way; I got pulmonary hypertension and chest pain from a very high dose of 5-HTP (~1 gram) once as well a long time ago. In addition to heavy nausea to the point of almost vomiting and severe somnolence, it was quite an unpleasant experience.

In any case, I'd recommend discontinuing the citalopram and talking to your doctor about it again immediately. Perhaps you should print out this post, show it to him, maybe have him reported to his superiors, and tell him to go back to ****ing school.

Good luck.

By the way, for more information, see these three articles (especially the second one):

• Wikipedia - Pulmonary Hypertension.
• Wikipedia - Cardiac Fibrosis.
• Wikipedia - Selective Serotonin Reuptake Inhibitor (SSRI): Adverse Effects. (scroll down a bit)

As well as these:

• Prescribing of Antidepressants in Cardiovascular Disease: A Study Using a Computerised General Practice Data Base.
• SSRIs and Persistent Pulmonary Hypertension [in Newborns].

[Medline]

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.

Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, 2400 N Pratt St, Box 3356, Durham, NC 27705, USA. oconn002@mc.duke.edu

BACKGROUND: Recent studies suggest that the use of antidepressants may be associated with increased mortality in patients with cardiac disease. Because depression has also been shown to be associated with increased mortality in these patients, it remains unclear if this association is attributable to the use of antidepressants or to depression. METHODS: To evaluate the association of long-term mortality with antidepressant use and depression, we studied 1006 patients aged 18 years or older with clinical heart failure and an ejection fraction of 35% or less (62% with ischemic disease) between March 1997 and June 2003. The patients were followed up for vital status annually thereafter. Depression status, which was assessed by the Beck Depression Inventory (BDI) scale and use of antidepressants, was prospectively collected. The main outcome of interest was long-term mortality. RESULTS: Of the study patients, 30.0% were depressed (defined by a BDI score > or =10) and 24.2% were taking antidepressants (79.6% of these patients were taking selective serotonin reuptake inhibitors [SSRIs] only). The vital status was obtained from all participants at an average follow-up of 972 (731) (mean [SD]) days. During this period, 42.7% of the participants died. Overall, the use of antidepressants (unadjusted hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.03-1.69) or SSRIs only (unadjusted HR, 1.32; 95% CI, 0.99-1.74) was associated with increased mortality. However, the association between antidepressant use (HR, 1.24; 95% CI, 0.94-1.64) and increased mortality no longer existed after depression and other confounders were controlled for. Nonetheless, depression remained associated with increased mortality (HR, 1.33; 95% CI, 1.07-1.66). Similarly, depression (HR, 1.34; 95% CI, 1.08-1,68 rather than SSRI use (HR, 1.10; 95% CI, 0.81-1.50) was independently associated with increased mortality after adjustment. CONCLUSION: Our findings suggest that depression (defined by a BDI score > or =10), but not antidepressant use, is associated with increased mortality in patients with heart failure.

[euphoria]

Originally Posted by rocknroll714

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.

[rocknroll714]

Originally Posted by euphoria

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.

Agreed. I found rebound to somewhat more fun than when I was actually under mirtazapine's influence while it was still in my system. Hence, the occasional incidence of hypomania or mania upon discontinuation with many patients.

[RockiNToM]

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.

[euphoria]

Isn't buspirone a weak D2 antagonist?

[RockiNToM]

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