Ampyra, 4-AP, 4-AP-3-MeOH

Dalfampridine, or Ampyra, is a potassium channel blocker that is shown to improve visual function, motor skills and relieve fatigue in MS patients.
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jennyms
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Ampyra, 4-AP, 4-AP-3-MeOH

Post by jennyms » Fri Dec 27, 2019 10:51 pm

Hello everybody.

It's my first post here, I have only recently discovered this site, and I have to say, it is a Godsend. I’ve been reading through the posts and I thought I’d make my own,

I have been suffering spasticity for five years now and it was only last three years that I made any progress in treating it.

Ampyra was far too expensive, in my opinion, and the amount that my insurance begrudgingly would pay for, the daily doses quite frankly did next to nothing to help my mobility.

So, then I turned to Google and discovered compounded 4-AP.

I got a prescription from my doctor (even though he'd never heard of it). I couldn't get insurance to pay for it, but it is cheap enough, so I paid 100%.

I had never even heard of a compounding pharmacy, I picked one and ordered some capsules.

Here's what I think:

Instant release 4-AP

Comes on quick. I like that. Empty stomach, and I am up and moving within 20 minutes.

Extended release 4-AP

Never works. Not if you ask me. Takes longer to kick in, then it comes on all at once like instant release.

Both instant and Extended release 4-AP

I have really noticed, after buying from numerous pharmacies, that, depending on the compounding, the effects are different. Or maybe it's the care and attention they put into the whole process, or the filler used. I don't know, but different pharmacies, different effects. I have even done side-by-side comparisons with different pharmacy's 4-APs and I stand by this.

I like 4-AP, it works very well, and it allows me to do a lot of things. Walking, obviously. Wiggle my toes. Helps my constipation. Eases my neuropathy, and pain (to a certain extent).

I wouldn't go back to Ampyra, even if it was the same price as 4-AP. It would be nice to take one pill twice per day, but I don't think it really works that way. Not for me, anyway. I am happy to take multiple 4-AP doses, as and when. Works, works quick, and on demand. And if I am inactive for a period, I can take a rest from the 4-AP.

4-AP-3-MeOH

I discovered 4-AP-3-MeOH early this year and I have been taking it ever since. Though, it is expensive, so when I run out, I return to 4-AP. I discovered it after googling around for spasticity medications, I read about it on forums for spasticity caused by other diseases. It doesn’t surprise me that there are numerous posts about 4-AP-3-MeOH here. I am, actually surprised that there aren’t more posts.
I am not sure if links are allowed here, I’ll wait to see if there are any replies saying yes or no, but I read on other forums and I Googled scientific reports about 4-AP-3-MeOH and I bought some capsules.
I didn’t really know what to expect, because all I really knew was 4-AP and Ampyra, but I was very impressed with the effects of 4-AP-3-MeOH. I’ll try and describe.
Walking,
On 4-AP, I can only walk quick, and people better get out of my way, because it has to be quick, and it has to be in a straight line. And my walking is highly robotic.

On 4-AP-3-MeOH.I have so much more control. I can walk slow, I can stroll. I can stop and balance, pivot on one foot and do a sharp 90 degrees. I can even stand on one leg (for a short time).
Balance.
On 4-AP, My balance is just as bad as without it. 4-AP only excels if I am walking at a rapid clip.
On 4-AP-3-MeOH.My balance is fantastic. I can close my eyes and not fall over. I can board a busy subway train and carefully manoevre my way to a space. Like I said, I can stand on one leg (short time). I tried some standing yoga poses, still fall over, but I can do a lot better than on 4-AP.
Sensation.
On 4-AP,I can feel something like a someone touching the sole of my foot (which I couldn’t otherwise feel, my feet feel dead.).
My fingertips usually feel dead, like covered in extremely thick skin. With 4-AP, I can actually feel through my fingertips, like if I push my thumbnails into my fingertips, I can feel the nails digging it.
On 4-AP-3-MeOH,it is completely different. I can feel the lightest sensations. Like someone touching the sole of my foot with the head of a pin, or stroke with a feather.
Maybe that’s why it helps balance so well. Signals going back and forth, reacting either way.

With 4-AP-3-MeOH, it is like I have no problem with my fingers at all. I can move my normally stiff fingers in a much more fluid manner, and my fingertips feel perfectly OK, no numbness whatsoever.
Constipation.
4-AP helps, 4-AP-3-MeOH not so much.
Neuropathy/pain.
I’d say they are about the same.
Overall physical effects.
Without a doubt, the 4-AP-3-MeOH is so much more comfortable to take than the 4-AP. Almost unnoticable. The 4-AP can feel brutal at times, especially on an empty stomach. 4-AP-3-MeOH feels, I don’t know, smooth, gentle. Maybe it’s the lower dose, maybe because it’s a different chemical, maybe both.

I’ve gone on enough now. But I’d like very much to talk with anyone who has successfully treated their spasticity. I’d especially like to know if anyone else takes/has taken 4-AP-3-MeOH and what your experiences were.
I’ll talk to you all soon.
Jenny.
xxx

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NHE
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Re: Ampyra, 4-AP, 4-AP-3-MeOH

Post by NHE » Sat Dec 28, 2019 7:38 am

Welcome to ThisIsMS. Thanks for sharing your experience.

PeterX
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Re: Ampyra, 4-AP, 4-AP-3-MeOH

Post by PeterX » Mon Dec 30, 2019 5:21 am

Hello jennyms,
thank you for sharing your experiences. I am taking Fampyra (The Biogen version of Ampyra in EU) for 2 years. I am SPMS and Fampyra helps me with moving even though I am on the wheelchair.
Fampyra is also quite expensive in my country (no insurance covers it). So I am also looking for alternative product to Fampyra and 4-AP-3-MeOH looks very promisingly for me. Please would you write me, where one can buy 4-AP-3-MeOH and whether for buying 4-AP-3-MeOH a prescription is needed?

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NHE
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Re: Ampyra, 4-AP, 4-AP-3-MeOH

Post by NHE » Tue Dec 31, 2019 9:27 pm

Novel potassium channel blocker, 4-AP-3-MeOH, inhibits fast potassium channels and restores axonal conduction in injured guinea pig spinal cord white matter.
J Neurophysiol. 2010 Jan;103(1):469-78.
  • We have demonstrated that 4-aminopyridine-3-methanol (4-AP-3-MeOH), a 4-aminopyridine derivative, significantly restores axonal conduction in stretched spinal cord white-matter strips and shows no preference in restoring large and small axons. This compound is 10 times more potent when compared with 4-AP and other derivatives in restoring axonal conduction. Unlike 4-AP, 4-AP-3-MeOH can restore axonal conduction without changing axonal electrophysiological properties. In addition, we also have confirmed that 4-AP-3-MeOH is indeed an effective blocker of I(A) based on patch-clamp studies using guinea pig dorsal root ganglia cells. Furthermore, we have also provided the critical evidence to confirm the unmasking of potassium channels following mechanical injury. Taken together, our data further supports and implicates the role of potassium channels in conduction loss and its therapeutic value as an effective target for intervention to restore function in spinal cord trauma. Furthermore, due to its high potency and possible low side effect of impacting electrophysiological properties, 4-AP-3-MeOH is perhaps the optimal choice in reversing conduction block in spinal cord injury compared with other derivatives previously reported from this group.

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Re: Ampyra, 4-AP, 4-AP-3-MeOH

Post by NHE » Tue Dec 31, 2019 9:54 pm

Acrolein-mediated conduction loss is partially restored by K⁺ channel blockers.
J Neurophysiol. 2016 Feb 1;115(2):701-10.
  • Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K(+) channels due to myelin damage leads to conduction block, and K(+) channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K(+) channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K(+) channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases.

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