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Re: ANYONE ON SELEGELINE? QUESTIONS... hok

Posted by SLS on February 16, 2003, at 22:37:46

In reply to Re: ANYONE ON SELEGELINE? QUESTIONS... SLS, posted by hok on February 16, 2003, at 12:53:03

Hi Hok.

(I didn't proofread this).

You've asked important questions for which I have no answers or understanding, but I'd like to clarify a few points.

> I am currently deciding whether to try use the selegiline tablets or the sublingual form as an augmentor. Until this point, I assumed the sublingual form was the obvious choice since it bypasses the 1) GI tract, 2) keeps more of the active form in the bloodstream and less of its metabolites floating around -- so hopefully less side effects.

I wasn't aware that there was a sublingual preparation available. It looks good to me on paper. Which side effects do you attribute to the metabolites? What type of dosing schedule would you use (dose x frequency)? Where do you get sublingual selegiline?

> But your theory on the antidepressant effects being due to the methamphetamine metabolite instead of the MAO-B inhibitory effect makes me think I should try the tablet form.

Actually, I tend to believe that it is the inhibition of MAO-A that occurs at dosages greater than 10mg that is most responsible for the type of global improvement that one looks for when treating moderate to severe depression. Unbeknownst to many is that MAOI-A metabolizes dopamine as well as norepinephrine and serotonin. As an augmentor of other antidepressant drugs, it would appear that certain people benefit from lower dosages of selegiline: 2.5 - 5.0mg.

Perhaps the inhibition of MAO-B is sufficient to complement the actions of the antidepressant drugs it supplements. However, I think it is important to recognize the extent to which selegiline is converted to stimulating metabolites, methamphetamine and amphetamine. N-desmethylselegiline is the third major metabolite of selegiline oxidation. Transdermal delivery yields a reduced amount of these metabolites combined as compared to the oral preparation. However, the metabolism of selegiline is shifted away from the inactive N-desmethyl product and toward the two amphetamines. I think these stimulants help account for the utility selegiline has in treating ADD/ADHD or CFS. In addition, stimulants sometimes function well as augmentors of antidepressants. I am not saying that MAO-B inhibition is without effect in the treatment of these illnesses, but I think it is more productive to take into account the presence of its metabolites and the ability of MAO-A to metabolize dopamine in order to understand the pharmacology of selegiline.

> On a side note, I've been a smoker in the past, and I always believed that the strong anti-anhednonic effect I've always gotten from it was due to the MAO-B inhibition involved.

Although smoking can reduce the activity of MAO-B located on blood platelets, I don't know to what extent such is reflected in the brain. As far as reducing anhedonia is concerned, I believe that this is explained by the observed increase in dopaminergic activity in regions of the brain involving reward (ie. nucleus accumbens) secondary to the stimulation of nicotinic ACh receptors by nicotine. Nicotine does not inhibit MAO-B.


---

"Platelet monoamine oxidase B activity is inversely associated with plasma cotinine concentration."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11082824&dopt=Abstract

---

"Smoking a single cigarette does not produce a measurable reduction in brain MAO B in non-smokers."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11072429&dopt=Abstract

---

"An acute dose of nicotine does not inhibit MAO B in baboon brain in vivo."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9674950&dopt=Abstract

---

"Brain reward system activity in major depression and comorbid nicotine dependence."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183688&dopt=Abstract

---

"Selegiline for the Delivery of Small Doses of Amphetamine in Autism, ADHD and Mental Retardation"

http://www.personalconsult.com/articles/selegilinedelivery.html

---


> Have a couple of questions, if you don't mind. Would like to hear more of your thought on the biochemical details of the atypical/anhedonia issue if possible, and what implications this has for taking either form of the drug.

Hmm. I have seen more than a few people here report that low dosages of oral selegiline have helped with anhedonia. However, I'm not entirely convinced that this anhedonia was integral to major depression or bipolar depression. It seemed to me that these reports came from people who were suffering from dysthymia or perhaps CFS. Soo... I don't know. However, for treating an episode of major depression or bipolar depression, I think it makes sense to regard selegiline as just another non-selective MAOI, and not to linger too long at lower dosages. If I were to give it a go, I would target somewhere between 40-60mg. Even if selegiline loses its selectivity at these dosages, it certainly does not make it a clone of Parnate or Nardil. It is a different drug that acts differently in the body, even if only subtly. For each of the irreversible MAOIs (tranylcypromine / Parnate, phenelzine / Nardil, isocarboxazid / Marplan, selegiline / Eldepryl), there are individuals for whom only one will work well.


> Also, what is the downside of the sublingual form? Does its pharmacokinetics fade very fast so frequent dosing is needed? Besides not having to administrate multiple doses throughout the day, what will be tha advantage of the patch over the sublingual form?

Great questions! No answers. Sorry.

> And lastly, have you had experience with either one personally? If so, can you relate your conclusions to us all? It would be much appreciated.

I tried Eldepryl (oral selegiline) over ten years ago. It did nothing for me, good or bad. However, having stopped at 30mg still leaves open the possibility that it might work well at the higher dosages now used. I would prefer to take some pills a few times a day than wear a patch every day for the rest of my life. However, people with major depression that have tried both preparations describe them as feeling like entirely different drugs, with the patch being unequivocally superior.

I'm going to follow your posts to see what you and others come up with. I am interested in revisiting selegiline.

Good luck!


- Scott

 

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