aquariusgirl
Senior Member
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@MartinK
I was just reading through this thread. Wow....very impressive results with Disulfiram.
Also, earlier you talked about diarrhea and other symptoms. I wondered if they could be related to disulfiram.
So DSF chelates copper and nickel .....so when patients on disulfiram forums complain of mast cell symptoms.. I wonder if the drug has chelated their copper, which is a cofactor for DAO which breaks down histamine.
Presumably, they would have to be pretty low in copper to begin with, so I'm making a couple of assumptions here.
DSF is apparently an inhibitor of the enzyme PAM, which is involved in the synthesis of signalling peptides, such as MSH, neuropeptide Y, VIP, etc...MSH has been documented to be low in CIRs patients. One symptom of low MSH is diarrhea, according to Dr Andrew Hayward.
https://www.ncbi.nlm.nih.gov/pmc/ar...-OmDVGKtFhAUSRsay5N4S2KHAGAgfbyACasx1zJErHKfk
Another poster on facebook outlined other issues with DSF, below.
- metabolites versus intact molecule, in vitro versus in vivo
- Tryptophol
- effect on Dopamine oxidation, Norepinephrine, and psych symptoms
- neurotoxic effects of accumulation of Dopamine and Norepinephrine aldehydes
- liver toxicity
- reduced metabolism of Acetaminophen, caffeine, and theophylline
1. Dr. Kim Lewis' in vitro study demonstrated eradication of Borrellia with Disulfiram. While interesting, this information is not useful clinically, because Disulfiram never reaches the blood stream. Instead, the metabolites are what reach the blood stream (S-methylN,N-diethylthiocarbamate and its sulfoxide, diethylamine, and carbon disulfide). It's possible one or more of these have antimicrobial activity.
Before experimenting with patients, why not do a simple in vitro study of the effectiveness of these metabolites (individually and in combination) on Borrelia persisters? If these metabolites work in vivo, they would have to work in vitro, but the converse is not necessarily true.
https://www.ncbi.nlm.nih.gov/pubmed/1471547
2. Disulfiram also produces Tryptophol in the liver. Tryptophol is believed to be genotoxic.
https://content.sciendo.com/.../aiht/62/1/article-p41.xml
3. Disulfiram reduces the oxidation of Dopamine, causing a possible increase in patient Dopamine levels. It also reduces levels of Norepinephrine in the brain. This can be beneficial in some cases, but seriously dangerous in those with mental health issues, depression, anxiety, etc or sensitivity to Dopamine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290718/
4. The inhibition of Aldehyde Dehydrogenase not only affects the metabolism of acetaldehyde (post ethanol) but also the aldehyde metabolities of Dopamine and Norepinephrine. These are neurotoxic substances. http://pharmrev.aspetjournals.org/content/59/2/125.long
5. Liver toxicity and injury. Perhaps ALT should be monitored weekly or bi-weekly. When Disulfiram was more commonly prescribed, it was likely the number 1 cause of medication induced liver injury.
https://livertox.nih.gov/Disulfiram.htm
6. Disulfiram reduces CYP450 2E1 and thus slows metabolism of Caffeine, Theophylline, and Acetaminophen. Attached is the Flockhart table which is useful for all medications to view substrates, inducers, and reducers.
https://drug-interactions.medicine.iu.edu/Main-Table.aspx
I was just reading through this thread. Wow....very impressive results with Disulfiram.
Also, earlier you talked about diarrhea and other symptoms. I wondered if they could be related to disulfiram.
So DSF chelates copper and nickel .....so when patients on disulfiram forums complain of mast cell symptoms.. I wonder if the drug has chelated their copper, which is a cofactor for DAO which breaks down histamine.
Presumably, they would have to be pretty low in copper to begin with, so I'm making a couple of assumptions here.
DSF is apparently an inhibitor of the enzyme PAM, which is involved in the synthesis of signalling peptides, such as MSH, neuropeptide Y, VIP, etc...MSH has been documented to be low in CIRs patients. One symptom of low MSH is diarrhea, according to Dr Andrew Hayward.
https://www.ncbi.nlm.nih.gov/pmc/ar...-OmDVGKtFhAUSRsay5N4S2KHAGAgfbyACasx1zJErHKfk
Another poster on facebook outlined other issues with DSF, below.
- metabolites versus intact molecule, in vitro versus in vivo
- Tryptophol
- effect on Dopamine oxidation, Norepinephrine, and psych symptoms
- neurotoxic effects of accumulation of Dopamine and Norepinephrine aldehydes
- liver toxicity
- reduced metabolism of Acetaminophen, caffeine, and theophylline
1. Dr. Kim Lewis' in vitro study demonstrated eradication of Borrellia with Disulfiram. While interesting, this information is not useful clinically, because Disulfiram never reaches the blood stream. Instead, the metabolites are what reach the blood stream (S-methylN,N-diethylthiocarbamate and its sulfoxide, diethylamine, and carbon disulfide). It's possible one or more of these have antimicrobial activity.
Before experimenting with patients, why not do a simple in vitro study of the effectiveness of these metabolites (individually and in combination) on Borrelia persisters? If these metabolites work in vivo, they would have to work in vitro, but the converse is not necessarily true.
https://www.ncbi.nlm.nih.gov/pubmed/1471547
2. Disulfiram also produces Tryptophol in the liver. Tryptophol is believed to be genotoxic.
https://content.sciendo.com/.../aiht/62/1/article-p41.xml
3. Disulfiram reduces the oxidation of Dopamine, causing a possible increase in patient Dopamine levels. It also reduces levels of Norepinephrine in the brain. This can be beneficial in some cases, but seriously dangerous in those with mental health issues, depression, anxiety, etc or sensitivity to Dopamine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290718/
4. The inhibition of Aldehyde Dehydrogenase not only affects the metabolism of acetaldehyde (post ethanol) but also the aldehyde metabolities of Dopamine and Norepinephrine. These are neurotoxic substances. http://pharmrev.aspetjournals.org/content/59/2/125.long
5. Liver toxicity and injury. Perhaps ALT should be monitored weekly or bi-weekly. When Disulfiram was more commonly prescribed, it was likely the number 1 cause of medication induced liver injury.
https://livertox.nih.gov/Disulfiram.htm
6. Disulfiram reduces CYP450 2E1 and thus slows metabolism of Caffeine, Theophylline, and Acetaminophen. Attached is the Flockhart table which is useful for all medications to view substrates, inducers, and reducers.
https://drug-interactions.medicine.iu.edu/Main-Table.aspx
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