Modafinil

Strike me lucky

Well-Known Member
The novel wake-promoting agent modafinil has been in use for the treatment of several sleep disorders for a few years and is now undergoing clinical trials for its use in the treatment of stimulant addiction, but its primary mechanism of action remains elusive. Previous laboratory studies have shown that modafinil has antioxidative and neuroprotective effects, which have not previously been suggested to be related to its wake-promoting effects. However, recent research indicates that free radicals may be related to sleep induction as well as cellular damage, suggesting that a common target of action may mediate modafinil’s ability to oppose both of these effects. In this review we summarize and discuss previously published research on modafinil’s neural, cytoprotective, and cognitive effects, and we propose possible primary biochemical targets that could underlie the effects of modafinil observed in these studies. We also suggest neurocognitive mechanisms responsible for modafinil’s cognitive enhancing effects and its therapeutic potential in the treatment of stimulant addiction.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/
 

Paw

Well-Known Member
This is really interesting. My neurologist prescribed modafinil in early December, but we've been battling Humana's refusal ever since. I had only known it to be a sophisticated stimulant, but reading of its neuroprotective properties makes me all the more eager to try it.
 

Strike me lucky

Well-Known Member
It does work on dopamine receptors which could be the reason its neuroprotective, as substances working on this receptor can have anti inflammatory effects.
Theres probably other mechanisms.
It may even help mitochondrial effects similar to k-pax.
It may help with cognititive issues in cfs/me by improving orthostatic symptoms.
 

Stavya

Administrator
Staff member
Mechanisms of modafinil: A review of current research


Neuroprotective effects of modafinil

Pierard et al (1995) measured the in vivo cortical pool of glutamate-glutamine, aspartate, inositol, and creatine-phosphocreatine using 2D COSY H-NMR. They found that modafinil increased the cortical pool of all of these substances and attributed modafinil’s neuroprotective effects to its ability to increase creatine-phosphocreatine and its wake-promoting actions to the resultant increased metabolic activation.
Antonelli et al (1998) tested modafinil’s neuroprotective effect with regard to glutamate cytotoxicity by measuring GABA release and GABA uptake in cultured rat cortical neurons. They found that unlike glutamate receptor antagonists, modafinil was unable to fully prevent initial reductions in GABA release, but modafinil was able to prevent the further reduction in GABA release over the following half hour that was seen in the cells exposed to glutamate but not modafinil. Modafinil also had no effect on GABA release or uptake in neurons not exposed to glutamate, indicating that modafinil does not simply stimulate additional GABA release; rather it may help cells recover their neurosecretory coupling mechanism after glutamate exposure.
Jenner et al (2000) looked at the neuroprotective and anti-parkinsonian effects of modafinil in monkeys treated with MPTP. In one study they found that the MPTP induced parkinsonism symptoms could be improved with modafinil 11 months after MPTP administration. In a second study they found that modafinil administration with MPTP was unable to prevent initial locomotor effects of MPTP, but was able to restore locomotor activity within two weeks. More nigral neurons survived when modafinil was administered in conjunction with MPTP. They concluded that modafinil stimulates locomotor effects in already injured animals, and modafinil is neuroprotective, but it does not effectively block the DA transporter, for it is not able to prevent the initial effects of MPTP which enters the cell through the dopamine transporter to cause damage.
Xiao et al (2004) used post mortem examination of the brains of MPTP treated mice. They found that modafinil reduced striatal GABA, increased the levels of reduced glutathione in MPTP damaged neurons, and reduced levels of the lipid peroxidation product malodialdehyde. These results suggest that modafinil exerts a neuroprotective effect through its ability to attenuate or prevent oxidative damage.
 

Paw

Well-Known Member
Safe to assume everything said of modafinil also applies to Nuvigil?

Coincidentally I just today received a letter from Humana indicating that they prefer Nuvigil over the generic modafinil (go figure). It gives me some hope I might still be able to try Nuvigil, if not Provigil.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
How close is modafinil to methylphenidate - does anyone know?
 

Strike me lucky

Well-Known Member
Safe to assume everything said of modafinil also applies to Nuvigil?

Coincidentally I just today received a letter from Humana indicating that they prefer Nuvigil over the generic modafinil (go figure). It gives me some hope I might still be able to try Nuvigil, if not Provigil.
Personal experiences i have read about nuvigil vs modafinil are mixed, some prefer modafinil and others nuvigil. I think one has to try both, i dont think newer is alwats better but it may be??
 

Strike me lucky

Well-Known Member
How close is modafinil to methylphenidate - does anyone know?
I had a friend who was prescribed dexamphetamine for his cfs. He gave me a few to try. The dose he was give i think was something like 5mg 3 times a day, he said 1 pill was more than enough. I took a half and was energetic speedy feeling all day and had a horrid time trying to sleep that night, so a very stimulant feeling. I gave it a few days and tried it again and it made me fall asleep, a few days later i tried it again and the same thing, i fell asleep. So a weird reaction for me.

I cant find the right words to describe modafinil but speedy isnt one. Mod is like turning neurons on in your brain where stims are like turning your neurons on and then making them dance?? For me i dont like that stimulant feeling but i guess for others they get a different reaction.
 

Who Me?

Well-Known Member
Wasn't modadinal first out for that disease where you fall asleep sitting up? For the life of me I can't remember what it's called. Help.

As far as I can remember it wasn't meant to be a stimulant like we think of Ritalin. It was supposed to keep those people from falling asleep but you could sleep on it if you wanted to.
 

Stavya

Administrator
Staff member
Wasn't modadinal first out for that disease where you fall asleep sitting up? For the life of me I can't remember what it's called. Help.
Narcolepsy.

As far as I can remember it wasn't meant to be a stimulant like we think of Ritalin. It was supposed to keep those people from falling asleep but you could sleep on it if you wanted to.
Yes, it was developed as a wakefulness-promoting drug (a.k.a eugeroic).
 

Paw

Well-Known Member
Well, just got Nuvigil approved, so I'll find out soon how helpful it might be.

FYI, Humana doesn't even list modafinil anymore on their comprehensive formulary (they did in December). Maybe they knew it was going away, and that's why they denied coverage in December. Their most recent denial letter added the criteria that patients had to have tried Nuvigil (unsuccessfully) before they'd consider modafinil. Thanks to a free-first-month coupon from Cephalon, I won't have to shell out my $500 deductible (for brand names) until next month -- after I determine whether I'm tolerant or not.

Lots of people seem to have success with mail-order modafinil made in India, but I'm squeamish about that option.
 

Who Me?

Well-Known Member
I tried to get modalert from Singapore but they wouldn't ship it because of the class of drug.

I have no problem trying meds from India or anywhere else. India is the leader in generics And probably a lot of what we take are from there anyway. I'm pretty sure @Strike me lucky gets his from India and he has no problems.

There are plenty of American drug manufacturers that have issues with their products. It's politicians who just want to scare us into paying quadruple for a drug from the U.S.
 
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Paw

Well-Known Member
Yeah, I have nothing against India (or most other countries for that matter). It's more the internet I don't know if I can trust. If I knew a certain company was good I'd probably try it -- although if Nuvigil works out for me, it'll wind up costing about $1.50 per day (including deductible), so I don't know how much bettter I'd do through the internet. (One India-sourced company that someone recommended seemed okay, but they talked about how they would replace "bad batches," which didn't make me feel very secure.
 

Who Me?

Well-Known Member
There are some really good overseas pharmacies that I've used and have had no problems with them or their products.

I think the problem would be finding one that ships modalert to the U.S. I found it for really cheap, I can't remember how much offhand, but they wouldn't ship to the U.S.

If you have an rx I wonder if it'd be cheaper in Canada? They may not be able to ship to the U.S. either though.

Oh and @Strike me lucky takes 25-50 mgs so you could split pills and see how that goes. He also has said he has tolerance issues sometimes.
 

tara

Member
<p>
There are some really good overseas pharmacies that I&#039;ve used and have had no problems with them or their products.</p><p><br /></p><p>I think the problem would be finding one that ships modalert to the U.S.&nbsp; I found it for really cheap, I can&#039;t remember how much offhand, but they wouldn&#039;t ship to the U.S. </p><p><br /></p><p>If you have an rx I wonder if it&#039;d be cheaper in Canada?&nbsp; They may not be able to ship to the U.S. either though.</p><p><br /></p><p>Oh and @Strike me lucky takes 25-50 mgs so you could split pills and see how that goes. He also has said he has tolerance issues sometimes.
</p><p><br /></p>
 

Strike me lucky

Well-Known Member
I got my modalert from an online pharmacy from singapore 200mgx10 for$8.50, and it seemed to work well. I was able to compare it to a locally bought modafinil from another friend who gets it prescribed and i couldnt tell the difference. The price was very different, i think from memory 30 x 100mg cost just over $100 and on top of that dr's fee's, i think it required seeing a psychiatrist here because its heavily regulated but everything seems to be here, just like dam melatonin and dhea and with a huge price increase.
 

Who Me?

Well-Known Member
There are some really good overseas pharmacies that I've used and have had no problems with them or their products.

I think the problem would be finding one that ships modalert to the U.S. I found it for really cheap, I can't remember how much offhand, but they wouldn't ship to the U.S.

If you have an rx I wonder if it'd be cheaper in Canada? They may not be able to ship to the U.S. either though.
@tara that gibberish is not showing on my phone in my original post or here. You must have gremlins.
 

Paw

Well-Known Member
Just FYI, to put a period on my Nuvigil experiment...

It only lasted about ten days. Started off promising, but side effects increased daily, until my neurologist told me to stop taking it (went to the urgent care to be sure mouth sores were not deadly).

Most discouraging was that, in addition to the mouth sores, the Nuvigil introduced me to my worst FM flare in a year or so. I could be wrong, but this relapse does not feel primarily like a "side-effect," but more like the Nuvigil had served as a trigger to a variety of symptoms that had been either contained or minimized by my duloxetine. (It even quickly stopped providing extra energy.)

I've been off the Nuvigil for nearly a week now, but the flare is still pretty much in full force. Hope it's not permanent!
 

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