Posted by Larry Hoover on November 21, 2004, at 12:17:11
In reply to Re: Sleep, selegiline and autoreceptors » Larry Hoover, posted by KaraS on November 12, 2004, at 14:46:38
> > > > Your hypothesis is that you have hypersensitive DA autoreceptors. You could look at the selegiline/DLPA experiment as a test of the null hypothesis.
> > > >
> > > > Lar
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> > >
> > >
> > > But I have taken selegiline and it does put me to sleep. That confirms the hypothesis, no?
> >
> > I dunno. I don't think you did the DLPA part, right?
>
> Even without the DLPA, selegiline shouldn't put me to sleep - if those autoreceptors aren't hypersensitive.There may be another explanation, why it puts you to sleep.
> > Sleep is a very complicated process. If you watch and listen to this flash presentation, you may get one of those intuitive aha's....
> > http://www.medscape.com/viewprogram/2791?src=search
>
>
> Ok, I admit it. I have no idea why you sent me that link. No intuitive ahas.I thought section 2, the detailed analysis of the complex network of different brain structures and neurotransmitters impinging on sleep, might have made something click.
> No concept of how this relates to my DA autoreceptor problem.
Maybe that's not the problem at all, eh?
> I assume, based on other things you wrote, that I'm supposed to understand from this how selegiline might help me - but I don't see it.
I thought you wanted it to deal with fatigue (which it would do, through stabilization of the mitochondrial membranes). The sleepiness thingie is a side-effect, in the greater scheme of things.
> > >My concern is could the continuous taking of selegiline do harm to the autoreceptors perhaps by making them more hypersensitive? I'd rather try to figure that out theoretically than empirically.
>
>
> I was thinking about this all wrong. The flooding of the synapses with dopamine is exactly what I need.Yes, your brain could have adapted to a deficiency in dopamine by becoming exquisitely autoreceptive. But again, I'm encouraging you to not close your mind on the subject. Theories are just that, theories. What else might explain your symptoms/response to meds? That should always be something being thought about, in parallel to your consideration of this one theory.
> > I don't know that you can. I'd wonder what led to hypersensitivity in the first place. Was it acute? Chronic? Did the situation remit/revert over time? (I.e. has the hypersensitivity gone away again?)
>
> > I can only shrug.
> >
> > Lar
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>
> I too wonder what lead to my hypersensitivity? Was I born that way? Could years of SSRI usage have given me this problem? Could it have been the CFS? A combination of the all of these things?Combination is most likely, though I lean to genes and CFS. I don't like blaming drugs, because if you weren't sick, you'd not have taken them at all.
> All I know is that I've had this for the past few months because over that time I've tried several stimulant type meds and supplements that have all, paradoxically, put me to sleep. I doubt it has gone away since my last recent trial but when I start on the selegiline again I will find that out. One thing I am certain of is that I will never know the answers to the questions of how long I've had this problem and what caused it.
Have you stayed on the meds for long enough to see if your body re-adapts?
> So the next step is to take measures to lessen the hypersensitivity. I think it makes sense to try the selegiline again with the DLPA this time as you have been urging. It's cheap, I tolerate it and I have all of the ingredients here at home already and if it works, I don't have to worry about the MAOI diet. My next questions to you now are:
>
> 1) The P-5-P I have also contains some B2 and 100 mg. of magnesium (in oxide and taurinate form). Is this a problem? Do I need to get pure P-5-P?I can't see why a little extra nutrition could possibly be a problem.
> 2) Can I take them DLPA, P-5-P and selegiline at the same time? (esp. if I take the selegiline sublingually) Or maybe I should take the selegiline at night ('cuz it sedates me) while taking the DLPA + P-5-P in the AM? Does it matter at all when they're taken?It only matters if you notice a difference. I wouldn't dream of trying to predict how you will react. I try to stay away from limiting my own thinking, in that way, about myself.
I'd suggest you use your intuition, and if you don't get the results you'd hoped for, you try another option from the list.
> 3) Do you know anything about the liquid selegiline citrate? I've read that it's better than the selegiline hydrochloride pills but I have a feeling that's more of a political issue than a therapeutic one.It's moot to me. Only the hydrochloride tablets available in Canada.
I suspect the sublingual preparations are better tolerated, and may avoid first-pass metabolism transformations. In gut uptake, the drugs run an enzyme gauntlet in the intestinal wall and mesentery, and then pass via the portal vein to the liver, where they get another shot at being enzymatically transformed. It looks like selegiline is substantially affected by first-pass metabolism, so I see this as a pharmacological issue, not a political one.
>
> Thanks,
> KWelcome,
Lar
poster:Larry Hoover
thread:387192
URL: http://www.dr-bob.org/babble/alter/20041108/msgs/418619.html