Darolutamide (odm-201), A Better Topical Than Enzalutamide?

[Sanchez1234]

No. Are you sure you're not imagining it from anxiety? Maybe go watch some TV and relax. Otherwise, perhaps this is what you get for rubbing experimental Chinese chemicals on your scalp. (You were warned.)

Besides continuing great hair growth and improved optimism in life due to that, the only thing I've noticed on daro has been skin/eye dryness which took weeks to develop at 10 mg twice daily.

When I put on my first batch I was elated. I felt so happy and excited because for me it felt like the beginning of the end of my hair loss suffering. And so far, it looks like it is exactly that.

But if you're feeling super stressed out and worried instead, perhaps you could be vulnerable to nocebo side effects. Kind of like when guys take one tablet of finasteride and then claim they have permanent erectile dysfunction.

Hope you feel better soon. Let us know.

Im quite calm, relaxing at home watching peaky blinders.

Tingling is as good as gone. Could be the dsmo or nothing at all. We will see tomorrow after 2nd dose.

I am quite exited i am trying something the could help. Was restless after finasteride and duta didnt work.

Will update after next dose.

 

[Sanchez1234]

Its the next morning for me. Still have a little tingling. Hasn't subsided since 12hours ago.

Because i would never get any hits with tingling and darolutamide i tried googling tingling and dsmo.
There is not much, but i found this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460663/ :

Dermatological studies with DMSO in humans have been scarce. The reason is not entirely clear because its application is not dangerous, rarely causing occasional side effects, such as itching, skin irritation, tingling or burning, and garlic odor from the breath.

So i hope it is the DMSO doing that.... anybody who used DMSO had somehing like this?

 

[Jonnyyy]

Its the next morning for me. Still have a little tingling. Hasn't subsided since 12hours ago.

Because i would never get any hits with tingling and darolutamide i tried googling tingling and dsmo.
There is not much, but i found this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460663/ :

Dermatological studies with DMSO in humans have been scarce. The reason is not entirely clear because its application is not dangerous, rarely causing occasional side effects, such as itching, skin irritation, tingling or burning, and garlic odor from the breath.

So i hope it is the DMSO doing that.... anybody who used DMSO had somehing like this?

How bad is the tingling?

 

[IdealForehead]

Its the next morning for me. Still have a little tingling. Hasn't subsided since 12hours ago.

Because i would never get any hits with tingling and darolutamide i tried googling tingling and dsmo.
There is not much, but i found this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460663/ :

Dermatological studies with DMSO in humans have been scarce. The reason is not entirely clear because its application is not dangerous, rarely causing occasional side effects, such as itching, skin irritation, tingling or burning, and garlic odor from the breath.

So i hope it is the DMSO doing that.... anybody who used DMSO had somehing like this?

Dubious. Keep in mind you've applied maybe 0.1 mL of dmso at most which is negligible. People that use dmso use much larger volumes topically.

I googled flutamide (better studied androgen receptive antagonist) tingling and i did find that listed as a rare side effect so possibly the daro is responsible.

But i can't think of a biological mechanism to explain it.

 

[Sanchez1234]

How bad is the tingling?

Not that bad, could live with it. I am more concerned about why and what it does to my healthy body.

 

[Sanchez1234]

Dubious. Keep in mind you've applied maybe 0.1 mL of dmso at most which is negligible. People that use dmso use much larger volumes topically.

I googled flutamide (better studied androgen receptive antagonist) tingling and i did find that listed as a rare side effect so possibly the daro is responsible.

But i can't think of a biological mechanism to explain it.

I googled it for enzalutamide as well: https://www.rxlist.com/xtandi-side-effects-drug-center.htm

The website mentiones:
- numbness/burning pain/tingling/prickly feeling under your skin

Especially tingling/prickly feeling under your skin is what i am experiencing. From my hands to my big toe. Not that intense and not everywhere at the same time.. but still.

And this as well: https://www.mayoclinic.org/drugs-supplements/enzalutamide-oral-route/side-effects/drg-20075790
- tingling of the hands or feet

 

[el_duterino]

In short, they're both androgen receptor antagonists meaning both work by blocking dht and testosterone from binding to androgen receptors. But darolutamide has a longer half life so will stay active in the scalp (and blood) longer and it blocks the androgen receptor probably somewhere around 62 to 186 times more strongly than RU.

Full strength comparison here:
https://www.hairlosstalk.com/intera...conversion-of-ru58841-to-darolutamide.109065/

The other primary difference is RU and its active metabolites can easily cross the blood brain barrier where daro cannot.

the longer half life is not how long it stays in the scalp - its how long it takes to be cleared once it enters the blood stream
anything longer than 1 hour is too long for long term hair maintenance s the side effects will be felt once it binds to other AR in the body

I used flutamide topically - it has a serum half life of 7 hours and not as powerful as RU but the side effects came quite strong after a few weeks of usage - basically very hard to maintain erections

For male pattern baldness you want the shortest serum life possible .

for the RU metabolites its only a very short fraction and no we dont have studies proving it passes the brain barrier

I have been using RU for 10 years and I am confident it did not give me the type of side effects I had on dutasteride or flutamide and I have a very active sex life

 

[IdealForehead]

the longer half life is not how long it stays in the scalp - its how long it takes to be cleared once it enters the blood stream
anything longer than 1 hour is too long for long term hair maintenance s the side effects will be felt once it binds to other AR in the body

I used flutamide topically - it has a serum half life of 7 hours and not as powerful as RU but the side effects came quite strong after a few weeks of usage - basically very hard to maintain erections

For male pattern baldness you want the shortest serum life possible .

for the RU metabolites its only a very short fraction and no we dont have studies proving it passes the brain barrier

I have been using RU for 10 years and I am confident it did not give me the type of side effects I had on dutasteride or flutamide and I have a very active sex life

El Duterino I've been using RU for 2 years as well at much higher dose than you have and I also have had no obvious side effects on RU due to its very low serum half life. So I agree it has a very clean side effect profile from my experience.

As for skin vs serum half lives, they are two separate but related things. I would encourage you to review the posts I made here and here on the subject.

Yes, in an ideal world, the serum half life should be very low to minimize potential side effects. However, when you have something with a very low serum half life, it will likely have a proportionately low skin half life (eg. retinoic acid as listed in those threads). Since RU has a serum half life of only 1 hour, it likely has a skin half life somewhere on the order of 5 hours at most, though this is just speculation based on data we have for other agents, as we have no measured data precisely on RU.

You have suggested you have maintained hair for many years on a very low dose of RU. If so you are lucky. I lost hair on much higher doses of RU than you. Everyone will likely have differing drug metabolism rates and also different degrees of androgen sensitivity. I think the short half life of RU means for many of us, the effect will wear off in the scalp too rapidly as well as it degrades.

I would definitely think RU makes a safer and better agent to try first for hairloss than something as strong and long lasting as daro. However, daro is giving me steady regrowth back on track to NW1, while RU at least up to 5% 2 mL twice daily (200 mg a day) did not.

Keep in mind flutamide easily crosses the blood brain barrier like traditional antiandrogens and daro only cross the blood brain barrier by 1.9–3.9%, so with a sufficiently low dose, daro should be relatively low risk (though not zero risk) for central side effects like sexual dysfunction. I have been on it a month and unlike cyproterone which neutered me in 2 weeks, my erectile function continues to improve on the daro. It is something I am continuing to watch.

My primary side effects on darolutamide (which I have been using at much too high doses) have been:

- Dry skin/eyes - was brutal at 10 mg twice daily, acceptable now at 6 mg/day.
- Mild appetite suppression - listed as a 5% side effect in the prior safety study.

Nothing too bad and I still intend to drop the dose further gradually over time.

We will need to get DMSO out of our solutions to reduce the systemic penetration, as DMSO facilitates deep penetration, which is likely not necessary for hair treatment. I will work on solving this next.

 

[sunchyme1]

El Duterino I've been using RU for 2 years as well at much higher dose than you have and I also have had no obvious side effects on RU due to its very low serum half life. So I agree it has a very clean side effect profile from my experience.

As for skin vs serum half lives, they are two separate but related things. I would encourage you to review the posts I made here and here on the subject.

Yes, in an ideal world, the serum half life should be very low to minimize potential side effects. However, when you have something with a very low serum half life, it will likely have a proportionately low skin half life (eg. retinoic acid as listed in those threads). Since RU has a serum half life of only 1 hour, it likely has a skin half life somewhere on the order of 5 hours at most, though this is just speculation based on data we have for other agents, as we have no measured data precisely on RU.

You have suggested you have maintained hair for many years on a very low dose of RU. If so you are lucky. I lost hair on much higher doses of RU than you. Everyone will likely have differing drug metabolism rates and also different degrees of androgen sensitivity. I think the short half life of RU means for many of us, the effect will wear off in the scalp too rapidly as well as it degrades.

I would definitely think RU makes a safer and better agent to try first for hairloss than something as strong and long lasting as daro. However, daro is giving me steady regrowth back on track to NW1, while RU at least up to 5% 2 mL twice daily (200 mg a day) did not.

Keep in mind flutamide easily crosses the blood brain barrier like traditional antiandrogens and daro only cross the blood brain barrier by 1.9–3.9%, so with a sufficiently low dose, daro should be relatively low risk (though not zero risk) for central side effects like sexual dysfunction. I have been on it a month and unlike cyproterone which neutered me in 2 weeks, my erectile function continues to improve on the daro. It is something I am continuing to watch.

My primary side effects on darolutamide (which I have been using at much too high doses) have been:

- Dry skin/eyes - was brutal at 10 mg twice daily, acceptable now at 6 mg/day.
- Mild appetite suppression - listed as a 5% side effect in the prior safety study.

Nothing too bad and I still intend to drop the dose further gradually over time.

We will need to get DMSO out of our solutions to reduce the systemic penetration, as DMSO facilitates deep penetration, which is likely not necessary for hair treatment. I will work on solving this next.

this forum should pay you to stay here man

 

[Sanchez1234]

Just applied 2nd dose and tingling a lot again 30 min later.

Anybody knows if i am hurting my body or of its a harmless side effect?

 

[Jonnyyy]

El Duterino I've been using RU for 2 years as well at much higher dose than you have and I also have had no obvious side effects on RU due to its very low serum half life. So I agree it has a very clean side effect profile from my experience.

As for skin vs serum half lives, they are two separate but related things. I would encourage you to review the posts I made here and here on the subject.

Yes, in an ideal world, the serum half life should be very low to minimize potential side effects. However, when you have something with a very low serum half life, it will likely have a proportionately low skin half life (eg. retinoic acid as listed in those threads). Since RU has a serum half life of only 1 hour, it likely has a skin half life somewhere on the order of 5 hours at most, though this is just speculation based on data we have for other agents, as we have no measured data precisely on RU.

You have suggested you have maintained hair for many years on a very low dose of RU. If so you are lucky. I lost hair on much higher doses of RU than you. Everyone will likely have differing drug metabolism rates and also different degrees of androgen sensitivity. I think the short half life of RU means for many of us, the effect will wear off in the scalp too rapidly as well as it degrades.

I would definitely think RU makes a safer and better agent to try first for hairloss than something as strong and long lasting as daro. However, daro is giving me steady regrowth back on track to NW1, while RU at least up to 5% 2 mL twice daily (200 mg a day) did not.

Keep in mind flutamide easily crosses the blood brain barrier like traditional antiandrogens and daro only cross the blood brain barrier by 1.9–3.9%, so with a sufficiently low dose, daro should be relatively low risk (though not zero risk) for central side effects like sexual dysfunction. I have been on it a month and unlike cyproterone which neutered me in 2 weeks, my erectile function continues to improve on the daro. It is something I am continuing to watch.

My primary side effects on darolutamide (which I have been using at much too high doses) have been:

- Dry skin/eyes - was brutal at 10 mg twice daily, acceptable now at 6 mg/day.
- Mild appetite suppression - listed as a 5% side effect in the prior safety study.

Nothing too bad and I still intend to drop the dose further gradually over time.

We will need to get DMSO out of our solutions to reduce the systemic penetration, as DMSO facilitates deep penetration, which is likely not necessary for hair treatment. I will work on solving this next.

How much do you think goes systematic? %

 

[whatevr]

I love when people who have low-grade hair loss come here and give advice. Consider yourself VERY lucky, just like the people who maintain for 15 years on Finasteride.
Do you think people would be using nuke-tier drugs if they could maintain with something as simple as RU or Propecia? We're buying and researching these untested drugs because we're masochists or something? There is no point being a concern troll and writing all these warnings while being a humble brag about how you maintained your hair for 10 years and still f*****g chicks left and right.

As far as the actual subject at hand..

It doesn't matter what RU's half-life is. What matters is that it is a piss-poor anti-androgen that is no longer developed for any purpose due to its low affinity that is outcompeted by DHT something like hundreds of times for its ability to bind to the AR. Once it is outcompeted on the first place you apply it (your scalp) it will then travel around the body and bind to whatever else it finds within those two hours of its precious half-life. Use RU consecutively for a few days at doses larger than 75 mg and then tell me about how you still even have a libido.

On the other side, a single dosage of Enzalutamide which has a half-life of 6 freaking days didn't impact my libido or cause gyno one bit, despite having an IC50 that is something like 60-70x (or more) lower than that of RU, and is only outcompeted by DHT about 2-3x.
How is that possible? Because due to the high affinity most of it bound to the first AR closest to the source of the application - which would be your scalp, exactly where you want it to. It's unfortunate that it also binds to GABA receptors, but that's where Darolutamide comes in! These drugs show that it is entirely possible to use very high affinity AR blockers topically and have success with a low profile of systemic (anti-androgenic) side effects, and that this is possible regardless of the half-life. Yes, it would be better if Darolutamide had a half-life of 30 minutes and not 10-15 hours, but a perfect drug is very hard to make.

In order for a drug to work as a hair loss topical the affinity is far more important than the half-life, because for a high affinity drug it is far more likely that it will bind close to where it is actually applied, which is what you want. You don't want it just falling through your scalp, not binding to anything due to being weak and then ending up in your bloodstream. Otherwise you may as well just take these drugs orally.

 

[whatevr]

Just applied 2nd dose and tingling a lot again 30 min later.

Anybody knows if i am hurting my body or of its a harmless side effect?

What is the vehicle you are using?

 

[Sanchez1234]

10 mL propanediol (or propylene glycol, or dipropylene glycol)
6 mL 94%+ ethanol
2 mL water
2 mL DMSO

50 mg daro is in this vehicle and i poured 1ml on my scalp.

 

[whatevr]

10 mL propanediol (or propylene glycol, or dipropylene glycol)
6 mL 94%+ ethanol
2 mL water
2 mL DMSO

50 mg daro is in this vehicle and i poured 1ml on my scalp.

Why the f^ck are we using DMSO with Darolutamide at all?

DMSO 80 mg/mL (200.57 mM)

Ethanol 38 mg/mL warmed (95.27 mM)

Water Insoluble
(http://www.selleckchem.com/products/odm-201.html)

We are talking about 0.1% solutions here, that is 1 mg/mL. Even unwarmed the ethanol will still probably dissolve at least 10 mg/mL. Just make the whole thing out of 96% ethanol and try it!

 

[Sanchez1234]

Why the f^ck are we using DMSO with Darolutamide at all?

DMSO 80 mg/mL (200.57 mM)

Ethanol 38 mg/mL warmed (95.27 mM)

Water Insoluble
(http://www.selleckchem.com/products/odm-201.html)

We are talking about 0.1% solutions here, that is 1 mg/mL. Even unwarmed the ethanol will still probably dissolve at least 10 mg/mL. Just make the whole thing out of 96% ethanol and try it!

As a financial guy , i have absolutely no knowledge of these vehicles. I'm just the dumb guinea pig who relies on people like you .

What do you suggest as a vehicle for 2.5mg (0.25%) daro?

 

[whatevr]

As a financial guy , i have absolutely no knowledge of these vehicles. I'm just the dumb guinea pig who relies on people like you .

What do you suggest as a vehicle for 2.5mg (0.25%) daro?

As I said above, based on the SelleckChem testing - ethanol 96% can probably handle that concentration easily. Try to make a pure ethanol vehicle. The mix should be completely transparent with no obvious clouding or particles. If you can achieve that, success! You don't need DMSO... and it should work.

On the other hand. A pure ethanol vehicle may dry too fast, in which case you could try the classic RU vehicle: 70% Ethanol and 30% PG.

 

[sunchyme1]

As I said above, based on the SelleckChem testing - ethanol 96% can probably handle that concentration easily. Try to make a pure ethanol vehicle. The mix should be completely transparent with no obvious clouding or particles. If you can achieve that, success! You don't need DMSO... and it should work.

On the other hand. A pure ethanol vehicle may dry too fast, in which case you could try the classic RU vehicle: 70% Ethanol and 30% PG.

when you gonna be trying this stuff yourself mate?

 

[whatevr]

when you gonna be trying this stuff yourself mate?

 

[Jonnyyy]

View attachment 71110

If for some reason i cant tolerate Darolutamide I wouldn't have a problem selling it to you for like 50% man, but I'm gonna try everything possible to make it work! Lol