Prochlorperazine

[Navid]

I was prescribed this for nausea but I'm finding it makes me feel better overall; mellows out my nervous system, reduces pain, helps sleep, increases appetite. Just overall seems to improve all my symptoms a bit. It is a D1 agonist. Does anyone have any ideas at all why this drug may make me feel so much better. Any advice, input appreciated.

Thanks.

 

[nandixon]

Prochlorperazine (Compazine) has too many potential modes of action to say for certain, but one of the more interesting possibilities is its theoretical use as a mast cell inhibitor. Do you have or suspect mast cell activation syndrome (MCAS)?:

Amitriptyline and prochlorperazine inhibit pro-inflammatory mediator release from human mast cells– Possible relevance to chronic fatigue syndrome

It is interesting that the tricyclic phenothiazine prochlorperazine, commonly used as an antiemetic, was also a potent inhibitor of human mast cell activation. The concentration of AMI and PRO shown here to effectively inhibit mast cell secretion is about 10 times higher than what might be expected from the maximal daily dose (e.g. assuming one compartment model for an 80 kg subject, the AMI max dose of 150 mg would yield a serum level of 6 μM). However, brain mast cells may be more susceptible to the action of AMI than the human cultured LAD2 leukemic mast cells.

 

[Navid]

Yes, I do have suspected MCAS so this may be why the med is helping. Thanks for your insight. I appreciate it.

 

[nandixon]

@Navid, The one time I tried prochlorperazine (for severe nausea) it made me much worse. So, two more possibilities for you (and again there are quite a few), based on mechanisms and drugs that are bad for me but which might be good for you instead are:

Its anticholinergic ability. Both huperzine A (a readily available OTC supplement) and mestinon (a common prescription drug for myasthenia gravis that's now also being used for POTS) have a strong anticholinergic action and both make me worse, so one or both might potentially be useful for you, especially if you suffer from POTS.

Its D2 receptor antagonist ability. There is a list of potential D2 receptor antagonists under the “Ligands” tab here:

https://en.wikipedia.org/wiki/Dopamine_receptor_D2

 

[Navid]

@Navid, The one time I tried prochlorperazine (for severe nausea) it made me much worse. So, two more possibilities for you (and again there are quite a few), based on mechanisms and drugs that are bad for me but which might be good for you instead are:

Its anticholinergic ability. Both huperzine A (a readily available OTC supplement) and mestinon (a common prescription drug for myasthenia gravis that's now also being used for POTS) have a strong anticholinergic action and both make me worse, so one or both might potentially be useful for you, especially if you suffer from POTS.

Its D2 receptor antagonist ability. There is a list of potential D2 receptor antagonists under the “Ligands” tab here:

https://en.wikipedia.org/wiki/Dopamine_receptor_D2

Thanks for this useful info. The prochlorperazine is one of only 3-5 drugs I have been able to tolerate since becoming ill. Everything else I have tried has made my symptoms worse. The drugs I can tolerate: Klonopin, lowers the excitoxicity of my nervous system, helps me to sleep and reduces symptoms when I am in a super severe flare. Fentanyl, given to help relieve extreme trigeminal nerve pain. The only pain reliever that took away pain and did not cause side affects. Do these drugs fit into the puzzle somehow too.

I can also tolerate very low doses of Propranalol when my heart races and I could take Tramadol for pain too. Every other thing I have tried from antibiotics, anti-virals, POTs/OI dugs, pain relievers, vitamins( D, C, B12, etc.) supplements, anti depressants, CBD have over stimulated my system and made all my symptoms worse, turning me into a complete non-functioning being.

Thanks for your help and insight.

What do you think of me trying the small dosage, 1mg, of Abilify that Stanford ME patients are having success with.

Thanks, Lisa

 

[nandixon]

What do you think of me trying the small dosage, 1mg, of Abilify that Stanford ME patients are having success with.

In theory, Abilify (aripiprazole) might be a good fit based on your experience with both prochlorperazine and Klonopin (clonazepam). All three of those modulate the dopamine D2 receptor in ways that are potentially complementary to one another.

 

[pattismith]

Prochlorperazine (Compazine) has too many potential modes of action to say for certain, but one of the more interesting possibilities is its theoretical use as a mast cell inhibitor. Do you have or suspect mast cell activation syndrome (MCAS)?:

Amitriptyline and prochlorperazine inhibit pro-inflammatory mediator release from human mast cells– Possible relevance to chronic fatigue syndrome

It may also have P2X7 inhibition potency:


https://www.ncbi.nlm.nih.gov/pubmed/23954492

Trifluoperazine and paroxetine may also be P2X7 inhibitors:

https://www.ncbi.nlm.nih.gov/pubmed/26341077

 

[Navid]

Trifluoperazine and paroxetine may also be P2X7 inhibitors.

@pattismith

So does this mean that one of those 2 drugs could help with our ME/CFS symptoms?

Thanks (science ignorant)

 

[pattismith]

Trifluoperazine and paroxetine may also be P2X7 inhibitors.

@pattismith

So does this mean that one of those 2 drugs could help with our ME/CFS symptoms?

Thanks (science ignorant)

yes it may be that Prochlorperazine, Paroxetine and Trifluoperazine could be helpful in our disease…
But!

-over activation of P2X7R in our disease is only a theory that need to be confirmed
-the studies about these drugs' ability to inhibit P2X7R are only in vitro and more investigations are needed
-these drugs are "dirty drugs", they have many many other activities and many side effects!

If you are lucky to feel better with Prochlorperazine, we cannot conclude anything about the disease you have, nor about the effect of this drug, it is just a great gift for you to have found something that can help!