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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 17 to 41 of 41. Go back in thread:
Posted by SLS on September 12, 2009, at 7:06:13
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 12, 2009, at 6:45:14
> Buspirone only temporarily decreases serotonin levels; they return back to normal within a couple of hours. So that probably couldn't provide a steady solution if your analysis is right.
>
> Remeron appears to be very sedating to most, not to mention its weight gain. I feel that sedation is likely to ruin the benefits of 5HT2A/C-antagonism.
>
> Cyproheptadine is an interesting drug, but also very antihistaminergic=sedative. Seems like a bit of a horse med, as we say in Holland.
>
> Your best bet may be the Prozac + buspirone. Personally, I do feel that stimulating drugs might help your symptoms. They can at least provide motivation and initiative, and perhaps make you happier as well.
>
> Unfortunately, stimulating meds usually have an anxiogenic effect on me. I sometimes feel biochemically stuck between lust for life + anxiety or lack of anxiety + apathy. I know I'm not the only one.
>
> It's too bad that pure 5HT2A/C-antagonists haven't found their way onto the market. It seems that they didn't do too well as antidepressants in the trials.It is unfortunate that the manner in which drugs are developed and brought to market currently provides no incentive to produce drugs that are active only as adjuncts to other drugs. A case in point would be gepirone, a 5-HT1a partial agonist. By itself, it did not seem to be robust as an antidepressant, but it would probably make a good augmentor for one. Another deficit is that compounds that have had their patents expire are not developed further to be marketed. An example of this would be ritanserin. It is a potent and selective antagonist of 5-HT2 receptors. Personally, I would like to have seen clorgyline brought to market as well. It is a MAOI that is specific for MAO-A.
- Scott
Posted by metafunj on September 12, 2009, at 10:22:10
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by SLS on September 12, 2009, at 7:06:13
I agree with you guys. It would be nice if your doctor could just choose the pharmacological mechanisms you need and create custom made medications. Maybe someday far in the future that will be possible, when targeting certain receptors becomes easier and health begins to outweigh profit.
I have heard that drugs with antihistamine properties can be sedating but I have a friend that takes Remeron at night and he's fine. I have read that the higher the dose of Remeron the more it stimulates noradrenic receptors and activates you.Maybe, you're right about the stimulant Brainbeard. I basically have no anxiety so I think I could handle the dopamine boost and it would probably help with the ADHD like symptoms I've had since quitting prozac.
I had read some of your posts on the anhedonia topic and had wondered why you didn't try a stimulant instead of going the serotonin route, but if it gives you anxiety that makes sense.
I'm taking Wellbutrin SR 150 twice a day now and so far it seems like it mainly works on noradrenaline, making me kinda edgy and easily startled but not really doing anything for the emotional blunting and cognitive problems yet.
I just wonder if 5mg prozac would give enough 5HT2C stimulation with little reuptake inhibition.
Posted by Brainbeard on September 13, 2009, at 3:49:15
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by metafunj on September 12, 2009, at 10:22:10
> I just wonder if 5mg prozac would give enough 5HT2C stimulation with little reuptake inhibition.
Prozac appears to be such a strong 5HT2C-antagonist that doses between 2.5 and 5mg certainly have a significant effect. For me, 5mg had a stronger antidepressant effect. I suspect that at such a dose, mild SRI will come into play.
Posted by metafunj on September 13, 2009, at 9:09:27
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 13, 2009, at 3:49:15
Thanks, maybe I'll try taking 5mg every other day to get 2.5. I could combine it with the wellbutrin I'm taking now. It would be like turning the heat on a pot from below and then put the lid on the pot, making it heat up faster.
Does prozac do anything at the 5 HT2A receptor? Have you found that drugs with 5 HT2A antagonism exert a strong dopaminergic effect?
Posted by Brainbeard on September 13, 2009, at 10:03:34
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by metafunj on September 13, 2009, at 9:09:27
> Does prozac do anything at the 5 HT2A receptor?
Yes, as an SSRI, Prozac blindly activates 5HT2A-receptors. That is to say, any SSRI tends to blindly stimulate ALL serotonin receptors including all subtypes. 5HT1A-activation may be one of the leading mechanisms behind the (S)SRI's success as antidepressants. 5HT2A-activation is not good, and is probably one of the main reasons for the SSRI's initial (and perhaps partly prolonged) side-effects of increased anxiety and agitation. I'm not sure what happens after sustained activation - down-regulation of 5HT2A-receptors? If so, long-term agonizing of 5HT2A-receptors may have the same outcome as 5HT2A-antagonism, namely (indirect) inhibition of
5HT2A-receptors putting a brake on dopamine and noradrenaline.>Have you found that drugs with 5 HT2A antagonism exert a strong dopaminergic effect?
>
Well, I have mixed experiences. Low dose Risperdal (0.5mg), a potent 5HT2A-antagonist, seemed to have some pronounced pro-dopaminergic effects on me.Low dose Geodon (ziprasidone, 5-60mg) was a bit of a disappointment since besides whatever good it was doing me, it also made me feel emotionally flat, which was the opposite of what I had hoped for.
I tried to take amitriptyline doses high enough to reach significant 5HT2A-antagonism, but the antihistaminergic sedation was too much for me to swallow.
Just 25mg of nortriptyline (amitriptyline's metabolite) did help my sleep a lot, combined with Luvox (fluvoxamine) and clomipramine, but I'm not sure if that was due to its mild 5HT2A-antagonism. It might well be. Could also be the NRI though.
Posted by metafunj on September 14, 2009, at 11:35:59
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 13, 2009, at 10:03:34
It's interesting that NRI would make you tired. I find it makes me kinda jumpy. I take wellbutrin and last night couldn't sleep, I may have to adjust the time I take the 2nd dose.
I have a friend who tried a lot of drugs and the only thing that worked was mirtazapine. Probably because of the 5HT antagonism along with 5ht1a agonism due to its serotonin boosting effects. He doesn't have any weight gain yet and says it doesn't make him tired, so I may try it in the future.
Posted by rgb on September 19, 2009, at 11:34:58
In reply to Re: The Final Pathway To The Dopaminergic Pot Of Gold?, posted by Sigismund on July 3, 2009, at 1:42:01
> Off the top of my head I wonder about very low dose Dexedrine and Ritalin with agomelatine at night.
Interesting idea (sadly, I don't have access to either...).
>
> I worry a bit about 5ht2A blockade. For some reason I feel better about 5ht2C. Probably some prejudice in favour of hallucinogens.Seconded. I was under the impression that 2A *increases* dopamine release and 2C decreases it, but I don't know where I got that impression :)
To confuse things further, apparently different agonists can activate the 2A receptor in different ways, explaining why only some of them cause psychedelic effects:
Posted by metafunj on September 19, 2009, at 21:06:50
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 12, 2009, at 6:45:14
Hey Brainbeard I had some questions.
Do you think taking Buspar + Prozac would cause movement disorders in the future due to buspar's D2 antagonism or do you think the increase in DA release from 5 HT2C antagonism would prevent this by increasing dopamine? I'm not sure if this increase is in the same place in the brain that would effect movement.
I've read about some people having dark moods on buspar. Do you have any idea why this could be? Do you think it could be from D2 antagonism or too much of a decrease in serotonin transmittion to other receptors?
If SSRIs cause indirect agonism of the 5HT1A receptor how come they don't cause the release of dopamine? It is said because SSRIs agonize the
5HT2A/C receptors they inhibit dopamine release, but Buspar taken with an SSRI can increase dopamine in spite of the indirect 5HT2A/C agonism. So if buspar acts just like serotonin, why wouldn't the indirect agonism of an SSRI increase dopamine release and decrease serotonin release similar to Buspar?The reason I ask about all this meds have caused such a problem in the past that I am fearful of the effects they could have long term. I'm starting to think a stimulant like provigil might be better, but i think it sure would be harder to get a script for.
Posted by Brainbeard on September 20, 2009, at 4:54:59
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G » Brainbeard, posted by metafunj on September 19, 2009, at 21:06:50
I think movement disorders or other extrapyramidal side-effects (EPS) are unlikely to be caused by Buspar. To date, I haven't heard of any case of Buspar caused EPS. The partial D2-antagonism is probably too weak for that. Especially when you take it at recommended doses, I don't think there will be a problem. In some trials, people have been taking doses of up to 1200mg of Buspar (as an antipsychotic), apparently without trouble.
5HT2C or -A-antagonism in itself can probably not (completely) prevent EPS; it seems that the reason that the atypical antipsychotics are less likely to induce EPS must rather be seen in their weaker adherence to D2-receptors.
> I've read about some people having dark moods on buspar. Do you have any idea why this could be? Do you think it could be from D2 antagonism or too much of a decrease in serotonin transmittion to other receptors?I think this is probably a temporary effect of the decrease in serotonergic tone that Buspar causes. It seems that some people experience a transient depressive phase while starting Buspar therapy.
> If SSRIs cause indirect agonism of the 5HT1A receptor how come they don't cause the release of dopamine?Good question. They very well might indirectly cause a release of dopamine, that might on the other hand be countered by their indirect agonism at 5HT2A/C-receptors.
> It is said because SSRIs agonize the
5HT2A/C receptors they inhibit dopamine release, but Buspar taken with an SSRI can increase dopamine in spite of the indirect 5HT2A/C agonism. So if buspar acts just like serotonin, why wouldn't the indirect agonism of an SSRI increase dopamine release and decrease serotonin release similar to Buspar?Indirect or direct agonism probably makes a big difference. Direct agonism of 5HT2B-receptors, for instance, is likely to cause heart valve damage. The ergoid dopamine-agonists are 5HT2B-agonists and carry this cardiac risk. The indirect 5HT2B-agonism of SSRI's, on the other hand, doesn't seem to cause this cardiovalvulopathy. Also, direct agonism of 5HT2A-receptors is likely to induce hallucinations. Still, the indirect agonism of 5HT2A-receptors by SSRI's is very unlikely to cause hallucinations. So apparently, there is a big difference.
Buspar is really a very mild medication that is practically free of serious side-effects. It can make you a little bit dizzy at medium-high doses (for me: doses above 10mg at a time). Personally, I don't even find this dizziness unpleasant.
If I were you, Buspar would be one of the last meds I would worry about. If it can help you, I would surely take it. It may take some time to reach full therapeutic effect, although in combination with Prozac the dopaminergic boost is immediate.
Posted by metafunj on September 20, 2009, at 8:13:50
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 20, 2009, at 4:54:59
Thanks for all the answers. They make perfect sense.
Since I am somewhat sensitive to drugs it good to take some precautions. I guess I'll just have to wait out this trial on Wellbutrin and see what happens.
Posted by metafunj on September 21, 2009, at 11:33:30
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G » Brainbeard, posted by metafunj on September 20, 2009, at 8:13:50
According to the abstract below, adding 5 HT1A agonism further enhances the release of dopamine induced by 5 HT2A antagonism. So just incase 5 HT2A blockage isn't enough to reach the pot of gold, 5 ht1a agonism may help get you there.
5-HT2A and D2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release.
Original Articles
Journal of Neurochemistry. 76(5):1521-1531, March 2001.
Ichikawa, Junji; Ishii, Hideo; Bonaccorso, Stefania; Fowler, Wiley L.; O'Laughlin, Ian A.; Meltzer, Herbert Y.
Abstract:
Atypical antipsychotic drugs (APDs), all of which are relatively more potent as serotonin (5-HT)2A than dopamine D2 antagonists, may improve negative symptoms and cognitive dysfunction in schizophrenia, in part, via increasing cortical dopamine release. 5-HT1A agonism has been also suggested to contribute to the ability to increase cortical dopamine release. The present study tested the hypothesis that clozapine, olanzapine, risperidone, and perhaps other atypical APDs, increase dopamine release in rat medial prefrontal cortex (mPFC) via 5-HT1A receptor activation, as a result of the blockade of 5-HT2A and D2 receptors. M100907 (0.1 mg/kg), a 5-HT2A antagonist, significantly increased the ability of both S (-)-sulpiride (10 mg/kg), a D2 antagonist devoid of 5-HT1A affinity, and R (+)-8-OH-DPAT (0.05 mg/kg), a 5-HT1A agonist, to increase mPFC dopamine release. These effects of M100907 were abolished by WAY100635 (0.05 mg/kg), a 5-HT1A antagonist, which by itself has no effect on mPFC dopamine release. WAY100635 (0.2 mg/kg) also reversed the ability of clozapine (20 mg/kg), olanzapine (1 mg/kg), risperidone (1 mg/kg), and the R (+)-8-OH-DPAT (0.2 mg/kg) to increase mPFC dopamine release. Clozapine is a direct acting 5-HT1A partial agonist, whereas olanzapine and risperidone are not. These results suggest that the atypical APDs via 5-HT2A and D2 receptor blockade, regardless of intrinsic 5-HT1A affinity, may promote the ability of 5-HT1A receptor stimulation to increase mPFC DA release, and provide additional evidence that coadministration of 5-HT2A antagonists and typical APDs, which are D2 antagonists, may facilitate 5-HT1A agonist activity.
Posted by Fivefires on October 28, 2009, at 11:31:51
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by metafunj on September 21, 2009, at 11:33:30
Might this 'pot of gold' be the answer to this horrible CFS?
I'm only on Effexor-XR and Xanax.
For supplements, B12 every 2wks, Folbic daily, D3 daily, an EFA, and a stress vite.
I have salt and sugar cravings; vicious cycle.
I'm withering.
Anyone?
forever 5f
Posted by Fivefires on October 28, 2009, at 11:36:06
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Fivefires on October 28, 2009, at 11:31:51
I forgot.
I stopped my thyroid replacement when realized it was exacerbating anxiety.
I see an endocrinologist in a couple weeks.
Might there be a test for adrenal fatigue? Might adrenal fatigue be the cause of CFS?
Can u use too much B12 or D3?
Shall I purchase some 5-HTP?
I need an answer so badly as I'm truly in a life or death state.
5f
Posted by metafunj on October 28, 2009, at 14:32:15
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Fivefires on October 28, 2009, at 11:36:06
Someone mentioned something called an Adrenal Stress test. Maybe your endocrinologist offers this, but you may have to see an alternative medicine practitioner. There is an alternative medicine board here and I wouldn't be surprised if some on that board are suffering from CFS.
Posted by Phidippus on November 2, 2009, at 14:56:42
In reply to The Final Pathway To The Dopaminergic Pot Of Gold?, posted by Brainbeard on July 2, 2009, at 16:14:09
Geodon (ziprasidone) is an interesting candidate for augmenting SSRI-therapy in a low dose - perhaps less than 20mg would already be enough?
Augmentation for what? Most studies show its efficacious for OCD in the 80 mg to 120 mg range.
I do 80 and get mood uplift and respite from my OCD.
P
Posted by Fivefires on November 2, 2009, at 16:45:39
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G » Fivefires, posted by metafunj on October 28, 2009, at 14:32:15
TU mj ..
I'll think about posting re: CFS on Alternatives board,
but to be honest with you, I don't think/feel
there will be anything I don't already know
which I can use
because of
FINANCIAL CONSTRAINTS - ONE OF THE REASONS I AM COMFORTED HERE ON PB,
I appreciate it.
5f
Posted by thinkingitover on November 22, 2009, at 15:26:04
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 20, 2009, at 4:54:59
> I think movement disorders or other extrapyramidal side-effects (EPS) are unlikely to be caused by Buspar. To date, I haven't heard of any case of Buspar caused EPS. The partial D2-antagonism is probably too weak for that. Especially when you take it at recommended doses, I don't think there will be a problem. In some trials, people have been taking doses of up to 1200mg of Buspar (as an antipsychotic), apparently without trouble.
>
> 5HT2C or -A-antagonism in itself can probably not (completely) prevent EPS; it seems that the reason that the atypical antipsychotics are less likely to induce EPS must rather be seen in their weaker adherence to D2-receptors.
>
> > I've read about some people having dark moods on buspar. Do you have any idea why this could be? Do you think it could be from D2 antagonism or too much of a decrease in serotonin transmittion to other receptors?
>
> I think this is probably a temporary effect of the decrease in serotonergic tone that Buspar causes. It seems that some people experience a transient depressive phase while starting Buspar therapy.
>
> > If SSRIs cause indirect agonism of the 5HT1A receptor how come they don't cause the release of dopamine?
>
> Good question. They very well might indirectly cause a release of dopamine, that might on the other hand be countered by their indirect agonism at 5HT2A/C-receptors.
>
> > It is said because SSRIs agonize the
> 5HT2A/C receptors they inhibit dopamine release, but Buspar taken with an SSRI can increase dopamine in spite of the indirect 5HT2A/C agonism. So if buspar acts just like serotonin, why wouldn't the indirect agonism of an SSRI increase dopamine release and decrease serotonin release similar to Buspar?
>
> Indirect or direct agonism probably makes a big difference. Direct agonism of 5HT2B-receptors, for instance, is likely to cause heart valve damage. The ergoid dopamine-agonists are 5HT2B-agonists and carry this cardiac risk. The indirect 5HT2B-agonism of SSRI's, on the other hand, doesn't seem to cause this cardiovalvulopathy. Also, direct agonism of 5HT2A-receptors is likely to induce hallucinations. Still, the indirect agonism of 5HT2A-receptors by SSRI's is very unlikely to cause hallucinations. So apparently, there is a big difference.
>
> Buspar is really a very mild medication that is practically free of serious side-effects. It can make you a little bit dizzy at medium-high doses (for me: doses above 10mg at a time). Personally, I don't even find this dizziness unpleasant.
>
> If I were you, Buspar would be one of the last meds I would worry about. If it can help you, I would surely take it. It may take some time to reach full therapeutic effect, although in combination with Prozac the dopaminergic boost is immediate.It's interesting that you bring this up with Buspar. I at one point had doubled my dose whilst on it and felt a sensation commonly associated with akathisia (severe restlessness, inner anxiety). My Pdoc said the same thing... not likely. I wonder what could have caused that, serotogenic or dopamine related....
Posted by mtdewcmu on November 26, 2009, at 0:02:04
In reply to Re: The Final Pathway To The Dopaminergic Pot Of G, posted by Brainbeard on September 12, 2009, at 6:45:14
Posted by conundrum on November 26, 2009, at 6:18:32
In reply to What about Serzone? (nm), posted by mtdewcmu on November 26, 2009, at 0:02:04
Could help, my psychiatrist takes that. I'd just be concerned about the rare liver toxicity. He told me that they believe the liver toxicity occured because of one contaminated batch, but it looks like britol myers squibb knew otherwise.
Anyway its a more potent 5-HT2 blocker than it is a reuptake inhibitor so it might work well.
Posted by mtdewcmu on November 26, 2009, at 10:36:57
In reply to Re: What about Serzone? » mtdewcmu, posted by conundrum on November 26, 2009, at 6:18:32
> Could help, my psychiatrist takes that. I'd just be concerned about the rare liver toxicity. He told me that they believe the liver toxicity occured because of one contaminated batch, but it looks like britol myers squibb knew otherwise.
>
> Anyway its a more potent 5-HT2 blocker than it is a reuptake inhibitor so it might work well.The liver failure supposedly happens once per 250,000-300,000 patient-years. That risk is comparable to the risk of dying in a railroad accident for a randomly chosen American. That's for any American, not just those that ride trains.(http://www.pbs.org/wgbh/nova/planecrash/risky.html)
Posted by conundrum on December 12, 2009, at 16:57:37
In reply to Re: What about Serzone?, posted by mtdewcmu on November 26, 2009, at 10:36:57
Well i saw that image on the site you linked to. It would seem to put things into perspective except most train accidents are well documented. The FDA believes the reports from nefazodone are only 10% of the actual number of incidents.
So would that make the risk 1 per 30,000 or 25,000 patient years? And what exactly is a patient year? If you're safe on it for 2 years does that mean your liver could still fall out on year 3?
Posted by mtdewcmu on December 15, 2009, at 21:52:35
In reply to Re: What about Serzone? » mtdewcmu, posted by conundrum on December 12, 2009, at 16:57:37
> Well i saw that image on the site you linked to. It would seem to put things into perspective except most train accidents are well documented. The FDA believes the reports from nefazodone are only 10% of the actual number of incidents.
>
> So would that make the risk 1 per 30,000 or 25,000 patient years? And what exactly is a patient year? If you're safe on it for 2 years does that mean your liver could still fall out on year 3?
I got that figure from the black box warning, which you can read at http://www.rxlist.com/serzone-drug.htmI believe the FDA had to have approved that warning.
A patient-year is equal to one patient taking the drug for one year. So, your risk of getting liver failure in any given year is 1 in 250,000 to 300,000.
If your liver has made it through two years, it may still fail on the third year, based on that statistic. If you want a better answer, you may want to ask a pharmacist or hepatologist.
Posted by mtdewcmu on December 31, 2009, at 1:22:03
In reply to The Final Pathway To The Dopaminergic Pot Of Gold?, posted by Brainbeard on July 2, 2009, at 16:14:09
The new antipsychotic Saphris is a fairly selective 5-HT2A and 5-HT2C antagonist. It would seem to be a good substance with which to put your theory to the test.
Posted by yasser on March 13, 2010, at 14:11:37
In reply to The Final Pathway To The Dopaminergic Pot Of Gold?, posted by Brainbeard on July 2, 2009, at 16:14:09
Posted by Deneb on March 20, 2010, at 15:22:34
In reply to Re: The Final Pathway To The Dopaminergic Pot Of Gold? (nm), posted by yasser on March 13, 2010, at 14:11:37
Hi Yasser!
Welcome to Psycho-Babble! I noticed your post doesn't contain any new information. I hope you didn't accidentally check the nm box after writing a long post!
Deneb
This is the end of the thread.
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