Fevipiprant Vs Setipiprant. Pgd2 Inhibitors.

[arnoldd]

Lets get back to the topic.
For topical we have to see, first, the molecular weight of each to see if it will reach the folicle. must be lower than 500 daltons ( g/mol) .
Fevipiprant : 426.41 g/mol
Setipiprant : 402.417 g/mol

So, it will go where it should. The second "problem " is if the drug will go systemic or not. That only can be know with an study. For example. Minoxidil goes in a really small %, ketoconazole ( at least 2 % ) don't go systemic , while other drugs like finasteride or dutasteride, go systemic in a high % .

Last one is to know the dosage, and that is also by experimentation . For example, minoxidil is used in a higher dose that the oral route, isotretinoin is use it in a lower dose topical than oral, so it also depend, basically, on each drug.

But the most important thing, the molecular weight, gives as the "ok"

Really Keto 2% dont go systemic ? neither a small quantity reach the bloodstream ?

Some stuff:

Fevi:
half life: ~20 hours
CRTh2 occupancy at 150mg >= 90%
Seti:
half life: ~10 hours

Pharmacokinetics:

Fevi
Seti

Information on fevi as a topical is discouraging and simultaneously insufficient. Basically the answer is oral and no reason is given.

I'm quite split between Citrizine HCL or Seti or Fevi + PGE2 It's going to have to be a topical because there is something else super important I need to save money for in December so I need to minimize cost, hence the desire for a topical.

Here's some other stuff: https://www.hairlosstalk.com/intera...hread-oral-once-a-day-pgd2-antagonist.103292/

Citrizine is the antihistaminic Ceterizine ? according to a study desloratadine seems work better than ceterizine because can prevent mast cell desgranulation which means less pro inflammatory mediators

 

[jamesbooker1975]

Really Keto 2% dont go systemic ? neither a small quantity reach the bloodstream ?



Citrizine is the antihistaminic Ceterizine ? according to a study desloratadine seems work better than ceterizine because can prevent mast cell desgranulation which means less pro inflammatory mediators

I can not find the original study , but here a coment on it :
https://rosacea-support.org/sebazole-topical-ketoconazole-gel-2.html
"An open-label study to evaluate the systemic absorption of ketoconazole in subjects applying ketoconazole USP 2% topical gel for the treatment of seborrheic dermatitis "
Basically, it was " hard" to detect any trace of ketoconazole after chronically use of 2 % ketoconazole gel .

About the Citrizine there is a new study done on topical for Androgenetic Alopecia :
https://www.ncbi.nlm.nih.gov/pubmed/28604133

 

[jamesbooker1975]

Some stuff:

Fevi:
half life: ~20 hours
CRTh2 occupancy at 150mg >= 90%
Seti:
half life: ~10 hours

Pharmacokinetics:

Fevi
Seti

Information on fevi as a topical is discouraging and simultaneously insufficient. Basically the answer is oral and no reason is given.

I'm quite split between Citrizine HCL or Seti or Fevi + PGE2 It's going to have to be a topical because there is something else super important I need to save money for in December so I need to minimize cost, hence the desire for a topical.

Here's some other stuff: https://www.hairlosstalk.com/intera...hread-oral-once-a-day-pgd2-antagonist.103292/

Where are you planning to buy all ? I checked alibaba, just curiosity, and only found two providers of Fevi, sent a message to one of them to get a quote, waiting for the reply.
thanks

 

[cocona]

Re
Citrizine is the antihistaminic Ceterizine ? according to a study desloratadine seems work better than ceterizine because can prevent mast cell desgranulation which means less pro inflammatory mediators

- See above post for related study. Cetirizine has few sides but overdose can be nasty. It's a gamble but there is definetely the possibility of the results scaling well at a higher % dosage especially considering how well certain other PGD2 inhibitors scale.

- Cetirizine has been tried as a hair loss remedy in forums before but the ones I saw were really low dosage derived from crushing tablets dissolving the Cet and decanting to get rid of the junk insolubles. Concentration was .33% Thread here.

- Many people talk about Ceritizine as a PGD2 inhibitor. This is the only paper I've found on the topic. They measured PGD2 inhibition at 50%. Furthermore only 60% of the patients experienced PGD2 inhibition. The authors hypothesize that the PGD2 is of mast cell origin. If this is true then this could be a limiting factor depending on the % of PGD2 in scalp produced by mast cells. I will need to look into mast cells since it is an area which I have neglected. With regards to Androgenetic Alopecia I have mostly focused on biochemical reactions.

- Cetirizine is sold by the kg so if I choose it and it pans out I will be good for as long as I wish to use it.

Where are you planning to buy all ? I checked alibaba, just curiosity, and only found two providers of Fevi, sent a message to one of them to get a quote, waiting for the reply.
thanks

Yeah I have to go Alibaba I'm not one of the cool kids. :-/ -sniffs-

 

[jamesbooker1975]

Some stuff:

Fevi:
half life: ~20 hours
CRTh2 occupancy at 150mg >= 90%
Seti:
half life: ~10 hours

Pharmacokinetics:

Fevi
Seti

Information on fevi as a topical is discouraging and simultaneously insufficient. Basically the answer is oral and no reason is given.

I'm quite split between Citrizine HCL or Seti or Fevi + PGE2 It's going to have to be a topical because there is something else super important I need to save money for in December so I need to minimize cost, hence the desire for a topical.

Here's some other stuff: https://www.hairlosstalk.com/intera...hread-oral-once-a-day-pgd2-antagonist.103292/

Also, keep in mind that half life, in this kind of drug, don't tell it all. Cause it all depend how long the seti or Fevi wi

- See above post for related study. Cetirizine has few sides but overdose can be nasty. It's a gamble but there is definetely the possibility of the results scaling well at a higher % dosage especially considering how well certain other PGD2 inhibitors scale.

- Cetirizine has been tried as a hair loss remedy in forums before but the ones I saw were really low dosage derived from crushing tablets dissolving the Cet and decanting to get rid of the junk insolubles. Concentration was .33% Thread here.

- Many people talk about Ceritizine as a PGD2 inhibitor. This is the only paper I've found on the topic. They measured PGD2 inhibition at 50%. Furthermore only 60% of the patients experienced PGD2 inhibition. The authors hypothesize that the PGD2 is of mast cell origin. If this is true then this could be a limiting factor depending on the % of PGD2 in scalp produced by mast cells. I will need to look into mast cells since it is an area which I have neglected. With regards to Androgenetic Alopecia I have mostly focused on biochemical reactions.

- Cetirizine is sold by the kg so if I choose it and it pans out I will be good for as long as I wish to use it.



Yeah I have to go Alibaba I'm not one of the cool kids. :-/ -sniffs-

I asked to one of the two sellers on alibaba ( Shanghai Handim Chemical Co ) A quotation for 20grams ofr fevi and all she asnwer me was " OK" ! .

 

[cocona]

Also, keep in mind that half life, in this kind of drug, don't tell it all. Cause it all depend how long the seti or Fevi wi

I asked to one of the two sellers on alibaba ( Shanghai Handim Chemical Co ) A quotation for 20grams ofr fevi and all she asnwer me was " OK" ! .

I was reading through this paper for like the 20th time and I noticed this part of it.

PTGDS is expressed in nonpermanent keratinocytes of the human hair follicle
In normal terminal human hair follicles, we found a similar presence of PTGDS, primarily in the nonpermanent hair follicle below the arrector pili muscle (Fig. 4A). However, staining was variable with many normal human follicles exhibiting little or no staining (Fig. 4B). This is consistent with lower levels of PTGDS mRNA in haired versus bald scalp and likely also reflects the lack of synchronicity in human hair follicle cycling. In miniaturized hair follicles in balding human scalp, sebaceous gland and hair follicle keratinocytes outside of the bulge (Fig. 4, C and E), and in some cases within the suprabasal bulge (Fig. 4D), expressed PTGDS. We also detected PTGDS outside of the hair follicle epithelium, indicating potential sources of PGD2 in the dermis (Fig. 4, E and F). In hair follicles undergoing catagen, PTGDS was present in mast cells within the fibrous streamer, which is the former site of the regressed follicle (Fig. 4E). These results in mouse and human demonstrate that the lipocalin PTGDS and its product PGD2 are predominantly expressed in the transient portion of the follicle at a time when the follicle begins regressing. These findings are in line with our hypothesis that the PGD2 pathway inhibits hair follicle growth.

We may be able to reduce PTGDS and as a result PGD2 by specfically targeting

1. Sebaceous gland hyperplasia (We can reduce this with Selenium Disulphide aka Selsun blue because selsun has been show to reverse sebaceous gland hyperplasia.)
2. Mast cells (We can lower this with Cetirizine)
3. Non permanent keratinocytes. (Just get the hairs growing again and this should stop being a problem)

Sure there are other things we can do but I mention these 2 because these are target-able with 2 easily found drugs:

Selsun blue is available in 1% in a shampoo or at prescription in a lotion at 2.5%. The prescription isn't needed however.

Because Ebay

Due to the half life of selenium in the body and that the lotion can actually go slightly systemic I wouldn't use it more than 2x/wk. Selenium has chronic toxic effects at around 2.5g in the body. Selenium has a terminal half life at around 1/wk.

Sidenote: you want the Selenium Sulfide version of selsun.

 

[folfoxorack]

But there some testimonies about hair loss after using selenium sulfide shampoos ...

 

[cocona]

But there some testimonies about hair loss after using selenium sulfide shampoos ...

Yeah that's true. It's a known although rare side effect.

I've been looking into this a bit. Here

It looks like it has some bad and good effects. Here is some stuff on the subject.

1. It increases 15-PGJ2 Via COX-1.( 15-PGJ2 is the bad sh*t that PGD2 turns into and actually induces catagen.)

"COX inhibitors and genetic knockdown approaches indicated that COX-1, and not the COX-2 pathway, was responsible for the increased synthesis of 15d-PGJ2 in Sesupplemented macrophages. Taken together, our results suggest that Sesupplementation increases the production of 15d-PGJ2 as an adaptive response to protect cells against oxidative stress-induced proinflammatory gene expression."

2. It decreases gene expression of PTGDS or at least I think that is what this is saying. I'm not super knowledgeable about gene transcription.

"Selenium (Se) is an essential micronutrient that suppresses the redox-sensitive transcription factor NF- κB-dependent proinflammatory gene expression"

3. The 15-PGJ2 is not a result of PGD2 isomerization with albumin like in this chart. By non enzymatic it means is not induced by PTGDS +PGH2 -> PGD2 + isomerization w/ albumin-> 15-PGJ2

"Here, we show for the first time that Se supplementation of macrophages leads to the preferential increase in 15d-PGJ2 via the arachidonic acid oxidation by COX-1, rather than COX-2. In macrophages and other immune cells, PGH2 is further converted to PGD2 by the hematopoietic PGD2 synthase (H-PGDS) that undergoes two spontaneous non-enzymatic dehydration reactions to form 15d-PGJ2 (29)."

I read the paper but most of it is lost on me. Looks like I need to learn more about immune response signaling because that might give some ideas of how to reduce PTGDS.

 

[arnoldd]

I was reading through this paper for like the 20th time and I noticed this part of it.



We may be able to reduce PTGDS and as a result PGD2 by specfically targeting

1. Sebaceous gland hyperplasia (We can reduce this with Selenium Disulphide aka Selsun blue because selsun has been show to reverse sebaceous gland hyperplasia.)
2. Mast cells (We can lower this with Cetirizine)
3. Non permanent keratinocytes. (Just get the hairs growing again and this should stop being a problem)

Sure there are other things we can do but I mention these 2 because these are target-able with 2 easily found drugs:

Selsun blue is available in 1% in a shampoo or at prescription in a lotion at 2.5%. The prescription isn't needed however.

Because Ebay

Due to the half life of selenium in the body and that the lotion can actually go slightly systemic I wouldn't use it more than 2x/wk. Selenium has chronic toxic effects at around 2.5g in the body. Selenium has a terminal half life at around 1/wk.

Sidenote: you want the Selenium Sulfide version of selsun.

Remember that pgd2 need to bind to his receptor d2 ( CRTH2) to cause inihbition in hair growth, we know the main source of pgd2 is mast cell and crth2 is upregulated when there is an allergic reaction or inflammation. i think the best strategy is prevent mast cell desgranulation which raise pgd2 and active crth2, so prevent any form of inflammation or allergic reaction and block the receptor crth2 (fevi).

however i don't understand a thing, i see a study where more estrogens are the result of more mast cell desgranulation, now all we know estrogens are good for hair growth....

 

[jamesbooker1975]

I was reading through this paper for like the 20th time and I noticed this part of it.



We may be able to reduce PTGDS and as a result PGD2 by specfically targeting

1. Sebaceous gland hyperplasia (We can reduce this with Selenium Disulphide aka Selsun blue because selsun has been show to reverse sebaceous gland hyperplasia.)
2. Mast cells (We can lower this with Cetirizine)
3. Non permanent keratinocytes. (Just get the hairs growing again and this should stop being a problem)

Sure there are other things we can do but I mention these 2 because these are target-able with 2 easily found drugs:

Selsun blue is available in 1% in a shampoo or at prescription in a lotion at 2.5%. The prescription isn't needed however.

Because Ebay

Due to the half life of selenium in the body and that the lotion can actually go slightly systemic I wouldn't use it more than 2x/wk. Selenium has chronic toxic effects at around 2.5g in the body. Selenium has a terminal half life at around 1/wk.

Sidenote: you want the Selenium Sulfide version of selsun.

Unfortunatly, Selenim Sulfide was dis

Yeah that's true. It's a known although rare side effect.

I've been looking into this a bit. Here

It looks like it has some bad and good effects. Here is some stuff on the subject.

1. It increases 15-PGJ2 Via COX-1.( 15-PGJ2 is the bad sh*t that PGD2 turns into and actually induces catagen.)



2. It decreases gene expression of PTGDS or at least I think that is what this is saying. I'm not super knowledgeable about gene transcription.



3. The 15-PGJ2 is not a result of PGD2 isomerization with albumin like in this chart. By non enzymatic it means is not induced by PTGDS +PGH2 -> PGD2 + isomerization w/ albumin-> 15-PGJ2



I read the paper but most of it is lost on me. Looks like I need to learn more about immune response signaling because that might give some ideas of how to reduce PTGDS.

What do you think on using Cetirizine oral ? I have asthma and antihistamine could be also beneficial on asthma ( I am using Frevia inhalator too ) . Yep, Fevi could be God send for me

 

[cocona]

Remember that pgd2 need to bind to his receptor d2 ( CRTH2) to cause inihbition in hair growth, we know the main source of pgd2 is mast cell and crth2 is upregulated when there is an allergic reaction or inflammation. i think the best strategy is prevent mast cell desgranulation which raise pgd2 and active crth2, so prevent any form of inflammation or allergic reaction and block the receptor crth2 (fevi).

however i don't understand a thing, i see a study where more estrogens are the result of more mast cell desgranulation, now all we know estrogens are good for hair growth....

Etsrogens have an effect of reducing PTGDS.

Something to consider: Evolution is not an engineer. The biochemistry of our bodies is excessively complex and inefficient. Nature is under no obligation to make our bodies make sense. You can totally have a series of effects for a specific input and have the net effect be bad or good for hair growth but have various good and bad effects. For example COX inhibition or Selenium disulphide.

 

[ALightInTheDark]

1. It increases 15-PGJ2 Via COX-1.( 15-PGJ2 is the bad sh*t that PGD2 turns into and actually induces catagen.)

Bad sh*t alert. To all of you,don't take that sh*t. If it increases 15-PGJ2,don't take it.

Remember that pgd2 need to bind to his receptor d2 ( CRTH2) to cause inihbition in hair growth, we know the main source of pgd2 is mast cell and crth2 is upregulated when there is an allergic reaction or inflammation. i think the best strategy is prevent mast cell desgranulation which raise pgd2 and active crth2, so prevent any form of inflammation or allergic reaction and block the receptor crth2 (fevi).

You're right. People here make the same mistake about DHT 'Block all the DHT of the body!!" no. You must absolutely not block all the DHT. Body needs DHT like PGD2 in normal dose. We need to NUKE this CRTH2 sh*t out of this mofo world and block/hakai it.
This is why simple PGD2 blockers don't make the trick : too weak to prevent PGD2 to bind to CRTH2 and start MBP process.
And that's why OC who nuke PGD2 is too dangerous with sleep side effects
Fevi Pulmagen and Seti are the best at blocking the CRTH2 recepetor.
I dream of a cheap CRTH2 everyday and everynight and to end this hair loss nightmare. We will care about regrowth later. You only saw Westonci good results with 2g in just one month and he didn't take minoxidil or anything..

Etsrogens have an effect of reducing PTGDS.

Where do you see that? I know that estro have anti androgenetic properties and raises FGF9. But PTGDS? Curious to see that

 

[cocona]

Swiss mentioned it on his reddit. I have't found anymore info on it yet.

"Do you think this will work for female hair loss? I assume prostaglandins are still influential even if its not strictly DHT related. Thank you

Yes of course it will. PGE2/PGD2 work the same way in both genders. Women usually just have more Estrogen which inhibits PTGDS somewhat (lower pgd2)."

 

[Ramsey]

What is people's experience with selenium disulfide - Selsun Blue - to inhibit Prostaglandin D2 synthase (PTGDS) and as possibly increase PGE2?

It's been discussed a bit in this thread, so I'd be interested if any of you have tried it or have heard about it? (Sorry, I don't want to push this thread in a different direction too much, maybe the selenium discussion deserves its own thread, but I can't start it because I'm a new member ;-).

I can't post links (those new member restrictions again), but there's a 1999 study by Hayashi showing that selenium chloride used into the third ventricle of a rat caused the rat to become sleep deprived as PGD synthase (PGDS), the enzyme responsible for the biosynthesis of PGD2 in the brain, was inhibited. And there's a 1997 study by Bell showing possible increase in PGE2 coming from it...

Afaik, the fear of selenium harming hair started way back from a very old study ("Effect of selenium sulfide suspension on hair roots", Archer, 1960) that shows "unequivocally" (their words) that selenium sulfide harms hair roots. It's an interesting study and a bit crazy in fact, plus it's also interesting to see how things were done back then, but it does seem odd. People definitely are worried still today about shock loss, so I've seen lots of advice to just use Selsun Blue quickly and only once a week or so. I haven't seen much good research on it from recent times, but Selsun Blue is still being sold, so I'm curious about selenium's real effects on hair.

 

[jamesbooker1975]

I finally got a quotation for fevipiprant in Alibaba. 980 usd per 1 gram ! .

 

[ALightInTheDark]

I finally got a quotation for fevipiprant in Alibaba. 980 usd per 1 gram ! .

Look at my post somewhere in page 5 or 6 I don't know maybe there is cheaper price in what I've post.
980$ is insane for 1 week. We need way cheaper Fevi since it'll be out in 1 year and half.
I was hoping for 10-12$ per gram at max lol..

 

[cocona]

What is people's experience with selenium disulfide - Selsun Blue - to inhibit Prostaglandin D2 synthase (PTGDS) and as possibly increase PGE2?

It's been discussed a bit in this thread, so I'd be interested if any of you have tried it or have heard about it? (Sorry, I don't want to push this thread in a different direction too much, maybe the selenium discussion deserves its own thread, but I can't start it because I'm a new member ;-).

I can't post links (those new member restrictions again), but there's a 1999 study by Hayashi showing that selenium chloride used into the third ventricle of a rat caused the rat to become sleep deprived as PGD synthase (PGDS), the enzyme responsible for the biosynthesis of PGD2 in the brain, was inhibited. And there's a 1997 study by Bell showing possible increase in PGE2 coming from it...

Afaik, the fear of selenium harming hair started way back from a very old study ("Effect of selenium sulfide suspension on hair roots", Archer, 1960) that shows "unequivocally" (their words) that selenium sulfide harms hair roots. It's an interesting study and a bit crazy in fact, plus it's also interesting to see how things were done back then, but it does seem odd. People definitely are worried still today about shock loss, so I've seen lots of advice to just use Selsun Blue quickly and only once a week or so. I haven't seen much good research on it from recent times, but Selsun Blue is still being sold, so I'm curious about selenium's real effects on hair.

I have some of the 2.5% lotion coming in the mail from Canada. It wont be here until Oct 16-26th though.

Basically it can recover hair or cause hair loss depending on the situation. It is probably a good idea if you are getting a lot of itching/inflammation/sweating in the scalp.

It will likely cause short term hair loss in certain follicles by triggering apoptosis in weakened follicles which are already about to hit catagen.

The short of it:
- Inhibits PTGDS transcription which has a side effect of increasing endogenous PGE2 since there will be more PGH2 available to turn into PGE2 due to less PGH2 being converted into PGD2

- Results in increased 15d-PGJ2 which triggers apoptosis in keratinocytes but not DP cells. (There is a lot more to this I might go into later. See Cotsarelis' paper for 2012)

 

[cocona]

What is it?

http://www.ebay.com/itm/Selsun-Blue...863598?hash=item25df94d76e:g:vvIAAOSw8w1YBDqB

 

[ALightInTheDark]

Fevipiprant is astronomically expensive(for now)

$938/1g

Private forum will make it to 4-500$ for 25g. So we need to do the effort to source it.
Seti is cheaper yes. But 2g a day? It's way too much. Fevi with 150mg is better. Fevi can't cost 50k/year since it'll be out in less than 2 years. These sellers are obviously scammers. I hope so coz it's very money dependent

 

[ALightInTheDark]

I have found this : https://books.google.fr/books?id=kB...IVTAH#v=onepage&q=9a 11b-pgf2 inhibit&f=false

It stated that "CRTH2 Activation : Decrease cAMP"

And guess what upregulates cAMP? https://www.ncbi.nlm.nih.gov/pubmed/6175546
"The increase in skin tyrosinase activity in response to UV was preceded by an increase in skin cAMP levels."
Also UVB is known to increase PGE2 by a lot.