Antipsychotic Drugs Inhibit Respiration

[haidut]

Most typical antipsychotics are anti-dopaminergic, and given dopamine's stimulating effect on respiration this study is not that surprising. The more important message is that anything that inhibits PDH is likely to be carcinogenic, so if possible avoid the drugs mentioned in the study.

http://www.ncbi.nlm.nih.gov/pubmed/1995086

"...The effects of 11 antipsychotic drugs on the pyruvate dehydrogenase complex (PDHC) prepared from bovine heart and rat brain were investigated. All inhibited PDHC to varying extents. With clinically equivalent doses, chlorpromazine and thioridazine inhibited the most and fluphenazine and thiothixene the least. The relationship of degree of inhibition of PDHC by neuroleptics to clinical improvement of 32 outpatients treated with acetazolamide and thiamine (A + T) ancillary therapy for chronic mental illness suggests that patients treated with psychoactive drugs that inhibit PDHC the least are most likely to have a favorable response with A + T treatment."

 

[mujuro]

haidut, did you come across any mention of atypicals being inhibitors as well?

 

[haidut]

post 99267 haidut, did you come across any mention of atypicals being inhibitors as well?

Nope, only the strictly anti-dopaminergic drugs seem to be implicated. Lower dopamine means higher levels of TPH and this higher serotonin, which has direct effects on PDH.

 

[mujuro]

post 99285

post 99267 haidut, did you come across any mention of atypicals being inhibitors as well?

Nope, only the strictly anti-dopaminergic drugs seem to be implicated. Lower dopamine means higher levels of TPH and this higher serotonin, which has direct effects on PDH.

Well the atypicals are anti-dopaminergic, just much less so. I am on quetiapine currently, at 300mg, however its D2 and D3 binding are so weak that normal elevations in dopamine are sufficient to displace the molecule from these sites. It also produces the lowest elevation of prolactin of all the atypicals which is probably a direct result of this very weak dopamine antagonism. Its strongest receptor binding affinity is to H1. Perhaps the anti-histamine action is one point in its favor, in a Peat context that is.

 

[haidut]

post 99505

post 99285

post 99267 haidut, did you come across any mention of atypicals being inhibitors as well?

Nope, only the strictly anti-dopaminergic drugs seem to be implicated. Lower dopamine means higher levels of TPH and this higher serotonin, which has direct effects on PDH.

Well the atypicals are anti-dopaminergic, just much less so. I am on quetiapine currently, at 300mg, however its D2 and D3 binding are so weak that normal elevations in dopamine are sufficient to displace the molecule from these sites. It also produces the lowest elevation of prolactin of all the atypicals which is probably a direct result of this very weak dopamine antagonism. Its strongest receptor binding affinity is to H1. Perhaps the anti-histamine action is one point in its favor, in a Peat context that is.

From what I understand, the main mechanism of action of atypicals is NOT dopamine. Hence, the name "atypical". So, even though they may have some affinity for the dopamine receptors it is considered clinically irrelevant. There are many case studies on PubMed showing anti-histamines and anti-serotonins inducing "remission" in psychotic conditions. Cyproheptadine is one such drug and mianserin is another.
Anyways, for the purpose of this discussion - I don't think atypicals affect respiration that much. For that, serotonin and prolactin are needed and the atypicals do not raise these much (as you mentioned).

 

[Noel Gallagher]

From what I understand, the main mechanism of action of atypicals is NOT dopamine. Hence, the name "atypical". So, even though they may have some affinity for the dopamine receptors it is considered clinically irrelevant. There are many case studies on PubMed showing anti-histamines and anti-serotonins inducing "remission" in psychotic conditions. Cyproheptadine is one such drug and mianserin is another.
Anyways, for the purpose of this discussion - I don't think atypicals affect respiration that much. For that, serotonin and prolactin are needed and the atypicals do not raise these much (as you mentioned).

Very dangerous haidut. In some psychosis situations, from excess t4 only treatment, for example, blood pressure rises and medications like cyproheptadine or mianserin will further raise metabolism and aggravate the existing psychosis.

 

[haidut]

Very dangerous haidut. In some psychosis situations, from excess t4 only treatment, for example, blood pressure rises and medications like cyproheptadine or mianserin will further raise metabolism and aggravate the existing psychosis.

Cyproheptadine and mianserin actually lower blood pressure. The issue with excess T4 is causing "thyroid storm" and that condition is different from psychosis for which the atypicals are given. So, yes, it is important to evaluate context before deciding on drugs. Again, the condition you are referring to is not the typical mental health psychosis and should not be called such. And the drugs for it would be different. Probably something to inhibit thyroid and an anti-adrenaline drug like clonidine, which has been used before for "thyroid storm" adrenergic crisis and the mental symptoms associated with it.

 

[Noel Gallagher]

Cyproheptadine and mianserin actually lower blood pressure. The issue with excess T4 is causing "thyroid storm" and that condition is different from psychosis for which the atypicals are given. So, yes, it is important to evaluate context before deciding on drugs. Again, the condition you are referring to is not the typical mental health psychosis and should not be called such. And the drugs for it would be different. Probably something to inhibit thyroid and an anti-adrenaline drug like clonidine, which has been used before for "thyroid storm" adrenergic crisis and the mental symptoms associated with it.

Okay. What other substances do you think would be helpful other than clonidine in a thyroid storm situation?

 

[haidut]

Okay. What other substances do you think would be helpful other than clonidine in a thyroid storm situation?

Beta blockers, cabbage/broccoli juice, 2g-3g NAC.

 

[Noel Gallagher]

Beta blockers, cabbage/broccoli juice, 2g-3g NAC.

Is the NAC just a one time dose?

 

[haidut]

Is the NAC just a one time dose?

Hopefully, but you may need to take for a few days depending on how severe thyroid storm is.

 

[Noel Gallagher]

Hopefully, but you may need to take for a few days depending on how severe thyroid storm is.

Okay. Is niacinamide a good option to help with the anxiety? Or would theanine be better? Or taurine?

 

[haidut]

Okay. Is niacinamide a good option to help with the anxiety? Or would theanine be better? Or taurine?

Pregnenolone, glycine, theanine, niacinamide are probably the safest and optimal.

 

[Noel Gallagher]

Pregnenolone, glycine, theanine, niacinamide are probably the safest and optimal.

Will those things further stimulate metabolism though?

 

[Noel Gallagher]

Pregnenolone, glycine, theanine, niacinamide are probably the safest and optimal.

And haidut, i just want to say I am so grateful for you and Danny Roddy's contributions. I love you guys. You guys are my heros.