Pendergast
Spain
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@leokitten how are you doing? Is your second chance with Abilify still working? (I hope so
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Abilify tolerance
- Thread starter Martin aka paused||M.E.
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pattismith
Senior Member
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Has anyone ever consider brain insulin resistance as a potential driver for Aripiprazole tolerance?
Antipsychotics differentially regulate insulin, energy sensing, and inflammation pathways in hypothalamic rat neurons - PubMed (nih.gov)
hmnr asg
Senior Member
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Let’s bring this thread back to life
Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone, Stove et al, 2022
In addition to ziprasidone there are other generic drugs people could try to inhibit VMAT2 for a while and possibly reverse Abilify tolerance.@leokitten how are you doing? Is your second chance with Abilify still working? (I hope so
My second cycle was still helpful until Nov 2022 when I had to stop. Didnt get to do a third cycle until this past March and it worked again though something different this time I had to take 2 mg per day instead of 0.5 and the effects came on in a more slow and smooth fashion compared to the first two cycles. Even though it came on slower it worked amazingly though I was able to go on a vacation for the first time in 3 years. But unfortunately this time LDA only worked for a little over a month before my ME symptoms came back in full. The need for a higher dose, the slower initial response, and the shorter response period all of this I still don’t understand maybe because I’m taking Prozac as well now.
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OMG I didn’t know fluoxetine is a known and pretty strong VMAT2 inhibitor! Ok wow maybe this is a theory as to why LDA didn’t work as long this third cycle
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I’m asking @jaybee00 the same question I think it’s in the other Abilify thread. He posted that valbenazine would be an idea to reverse Abilify tolerance in ME.
The problem with this idea is the user doesn't explain what is the basis for his theory as to why it would work.
Amisulpride is a D2/3 and 5-HT2B/7 antagonist. It has no efficacy at other receptors. For this reason I think something like ziprasidone, which is a D2/3/4 and 5-HT2A/2B/2C antagonist and 5-HT1A/1B/1D partial agonist, and I believe is a safer antipsychotic to use than amisulpride, would work similarly to reverse tolerance.
A useful paper to understand dopamine regulation and VMAT2:
Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease, German et al, 2015
"VMAT2 activity largely dictates quantal size, affecting the scale of subsequent neurotransmitter release" more than DAT or other methods of transportation into the synapse
Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease, German et al, 2015
"VMAT2 activity largely dictates quantal size, affecting the scale of subsequent neurotransmitter release" more than DAT or other methods of transportation into the synapse
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Here's some explanation. Probably has to do with taking low doses and blocking dopamine autoreceptors
https://psychscenehub.com/psychinsights/amisulpride-psychopharmacology/
https://psychscenehub.com/psychinsights/amisulpride-psychopharmacology/
I'm thinking the theory is that in pwME the initial triggering illness and immune response triggered permanent dopamine dysfunction and particularly hypofunction in at least part of our dopamine network and this is what contributes in a major way to PEM and fatigue.
Abilify is generally a D2 autoreceptor agonist in areas with low dopaminergic tone, and this agonism inhibits presynaptic dopamine synthesis and release. In full detail Abilify is a unique functionally selective agonist or antagonist depending on dosage and local dopaminergic tone. But in general I think that its presynaptic receptor agonism is what's thought to cause us tolerance after a few weeks to months.
Amisulpride is a D2 autoreceptor antagonist at low doses, which promotes presynaptic dopamine synthesis and release and this property is what I believe people think will reverse Abilify tolerance that has built up.
Abilify is generally a D2 autoreceptor agonist in areas with low dopaminergic tone, and this agonism inhibits presynaptic dopamine synthesis and release. In full detail Abilify is a unique functionally selective agonist or antagonist depending on dosage and local dopaminergic tone. But in general I think that its presynaptic receptor agonism is what's thought to cause us tolerance after a few weeks to months.
Amisulpride is a D2 autoreceptor antagonist at low doses, which promotes presynaptic dopamine synthesis and release and this property is what I believe people think will reverse Abilify tolerance that has built up.