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Dr. Bob is Robert Hsiung, MD,
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Posted by neo on October 26, 2005, at 13:42:15
Hi,
I have read on NCBI that neuroleptic agent produce Dopaminergic supersensitivity on DA receptor even after few application of a Neuroleptic agent.
What is the real meaning? The supersentivity inplicate more or less activity of the DA receptor? Is it like Tolerance or is it the opposite?
Thank you very much
Neo
Posted by lunesta on October 26, 2005, at 19:08:36
In reply to DOPAMINERGIC SUPERSENTIVITY: what is the meanig?, posted by neo on October 26, 2005, at 13:42:15
exactly, tolerance. You push on the dopamine receptor, it will push back much harder when you go off your neuroleptic. all artificial drugs that effect receptors usuallly do this. the terms tolerance, and withdrawl apply.
Posted by neo on October 26, 2005, at 20:15:24
In reply to Re: DOPAMINERGIC SUPERSENTIVITY: what is the meanig?, posted by lunesta on October 26, 2005, at 19:08:36
Thanks lunesta.
There any remedy for NOT DA receptor to develope quick tolerance?
In my experience, neuroleptic Amisulpride works great for the first 2 days than fade completely.
I think it could be probably the develope of tolerance on Da Presynaptic receptors (which are targeted by Amisulpride).
I am wrong?
Thanks to everybody!
neo
Posted by lunesta on October 26, 2005, at 21:23:06
In reply to Any remedy for DA Receptors Tolerance?, posted by neo on October 26, 2005, at 20:15:24
yousing the reverse antagonist of whatever receptor you are hitting will upregulate it, so taking an agonist will downregulate it.
example, a neuroleptic will upregulate the dopamine receptor, this isnt good for schizophrenics because they may never be able to get off.
to downregulate it, you would need to target the exact receptor with the opposite medicine which would antagonie it for a period of time and 'normalize it'
the perfect example is naltrexone, the opiate receptor antagonist. If you have tolerance to opiates, go off of them, then use naltrexone for the same period of time you used opiates or so, the receptors will upregulate and work again. so when you take codeine again after awhile, it will hit you hard, like you never took it before.
Amisulpride is interesting. At low doses it is a dopamine agonist, very similar to Survector actually. At higher doses, it is an antagonist. So you can play around with it a bit.
Posted by med_empowered on October 27, 2005, at 7:57:15
In reply to Re: Any remedy for DA Receptors Tolerance?, posted by lunesta on October 26, 2005, at 21:23:06
hey! Neuroleptic supersensitivity is kind of under-reported, and not very openly discussed. Its most studied with the old drugs (especially haldol). Here's how it works: patient takes Haldol. Haldol "occupies" large # of D2 receptor (70-90+ percent). Since the brain is getting such a tiny amount of dopamine, it springs up new dopamine receptors to compensate. This is part of the reason why its common to see people with schizophrenia start on a small dose of antipsychotic--say, 3mgs Haldol, 5mgs Zyprexa, etc.--and gradually progress to higher and higher doses just to control the hallucinations, so they may be taking 10mgs haldol or 15mgs zyprexa in a couple years. The drug-induced changes in the brain can lead to "supersensitivity psychosis"; some patients, given Thorazine and other drugs for depression, bipolar, or other non-psychotic disorders became floridly psychotic upon withdrawal of the drug..the psychosis went away once the drug was re-instated. The theory is that the brain can become so sensitive to its own dopamine that withdrawal of the neuroleptic results in a dopamine-overload leading to psychosis. Some studies have found that if you add an anti-convulsant mood-stabilizer to an antipsychotic you can reduce the "kindling" effects of the drug on the brain and keep the doses minimal. From what I understand, Abilify doesn't seem to induce dopamine supersensitivity, at least not to a great extent; apparently, because the agonist/antagonist action at both dopamine and serotonin kind of creates a sort of equilibrium, there are minimal long-term changes to the brain. And even with older antipsychotics, low-doses can sometimes be activating (ex: amisulpride, flupenthixol) instead of sedating; the super-low dose can result in increased reaction time and reduced apathy, while upping the dose can result in the "10 yard stare", lethargy, apathy, and general "dullness" we all associated with antipsychotics. Good luck!
Posted by neo on October 27, 2005, at 11:44:25
In reply to Re: Any remedy for DA Receptors Tolerance?, posted by med_empowered on October 27, 2005, at 7:57:15
Hi, Thanks Lunesta and Med_E for your interesting share.
In order to understand why Amisulpride works great for me for the first 2 days and than stop completely, I have found out, in a Solian (amisulpride)Product Monography, this abstract:
"This problem [Tolerance] is even more pronounced when changes in presynaptic DA release are taken into account. The onset of narcoleptic treatment activates negative feedback systems to produce a substantial increase in DA turnover. During chronic treatment, DA turnover in the accumbens does decrease from this elevated baseline, but the tolerance is only partial, and falls far short of reversing into an absolute decrease relative to the untreated state. (Galloway & Roth 1983 and Bowers 1985)."
So i have formulated my personal Hypotesys on this problem:
- The very first days Neuroleptic DA agonist (as amis and others) increase actually the Dopamine level, blocking non-sentivized pre-synaptic receptors.
- After few days receptors develope tolerance and the level of Dopamine greatly decrease but not down to baseline. Receptors are now sentivized.
- In few weeks the plus amount of dopamine begins to work and is acquired by the cells.It is ONLY my hypotesys. Do you think i am completely wronging?
That could explain why Neuroleptic (as DA agonist) works at the begin and than you must continue for several weeks to feel the positive effects.
Could anyone support or discuss my opinion?
Thanks in advance and excuse my incorrect English.
Neo
Posted by med_empowered on October 27, 2005, at 14:35:14
In reply to DA Receptors Tolerance and Neuroleptics. Opinion., posted by neo on October 27, 2005, at 11:44:25
I couldn't tell you...most of the supersensitivity stuff seems to be focused on patients receiving standard or high doses of neuroleptics for the control of psychosis. Again, if you're having problems with amisulpride, and you'd still like to try a neuroleptic, I'd recommend maybe giving abilify a shot...there's a problem with start up anxiety and akathisia, but other than that its a pretty clean drug (at low doses). As for reversing tolerance or preventing tolerance...I don't know what to say there, either. Tolerance seems to be an issue with all psychiatric meds, from antipsychotics to antidepressants to the stimulants and benzos. Sigh. Good luck.
Posted by blueberry on October 27, 2005, at 17:28:59
In reply to DOPAMINERGIC SUPERSENTIVITY: what is the meanig?, posted by neo on October 26, 2005, at 13:42:15
I know what you mean about early amisulpride tolerance setting in. A few years ago I tried it and got a nice dopamine rush for a couple days, which then faded away quickly. But I kept taking it anyway at 50mg. About 3 or 4 weeks later, I noticed I was becoming comfortable around people, relaxed, interested in things, non-depressed, and just feeling a lot better in general.
It's like that initial dopamine rush caused quick tolerance kind of like what would happen if taking a stimulant. But then over time, the extra dopamine floating around caused other changes in the brain that resulted in gradual overall improvements that were independent and separate from the initial dopamine rush of the first couple days.
Posted by SLS on October 27, 2005, at 17:37:19
In reply to Re: DOPAMINERGIC SUPERSENTIVITY: what is the meanig? » neo, posted by blueberry on October 27, 2005, at 17:28:59
Hi Blueberry.
> I know what you mean about early amisulpride tolerance setting in. A few years ago I tried it and got a nice dopamine rush for a couple days, which then faded away quickly. But I kept taking it anyway at 50mg. About 3 or 4 weeks later, I noticed I was becoming comfortable around people, relaxed, interested in things, non-depressed, and just feeling a lot better in general.
Are you still taking amisulpride?
- Scott
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Posted by neo on October 28, 2005, at 11:10:52
In reply to Re: DA Receptors Tolerance and Neuroleptics. Opini, posted by med_empowered on October 27, 2005, at 14:35:14
Thanks Med_ for your infos!
Unfortunely Abilify isn't available in my country and in other UE countryes is exxtremely expensive (ab. 10 $ a pill). Honestly, i can't afford this cost.
I will try to give a chance to Sulpiride. It seems to be more week than Amisulpride and so, perhaps, is possible that it will give less tolerance than that.
I will let you know....
Neo
Posted by blueberry on October 28, 2005, at 17:48:15
In reply to Re: DOPAMINERGIC SUPERSENTIVITY: what is the meanig? » blueberry, posted by SLS on October 27, 2005, at 17:37:19
Hi SLS,
It was years ago I tried amisulpride. I eventually gave it up for a couple reasons...I had also started prozac, and somehow the amisulpride jumpstarted the prozac so that the prozac worked fine without the amisulpride. It's almost as if the amisulpride reset things in the brain to last a good while even after stopping it. The main reason I quit was sexual dysfunction...amisulpride raises prolactin significantly.
Ever since my prozac and zypexa pooped out on me a few months ago, after 5 nice years, I've been in pretty bad shape. I tried amisulpride last weekend and it was great. I might just go for it again. It's kind of like my life preserver when things drag on too long without much improvement. Lexapro and depakote have been good for anxiety, but they do nothing for my depression. Amisulpride...very very tempting.
Posted by SLS on October 28, 2005, at 18:46:46
In reply to Re: DOPAMINERGIC SUPERSENTIVITY: what is the meanig? » SLS, posted by blueberry on October 28, 2005, at 17:48:15
Hi Blueberry.
Thanks for sharing your experiences with amisulpride. Perhaps I ought to place it higher on my list of things to try. I received a nice "kick" from sulpiride once. Unfortunately, it didn't last for more than a week.
I'm sorry to here that you are struggling. I hope amisulpride does the trick for you.
- Scott
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