Posted by Jason911 on March 4, 2002, at 19:17:10
Felt I should post this again. I just don't see how this could not be true. I'd believe a man as smart as Dr Joseph Knoll. He knows his shit.
"deprenyl's discoverer, Dr. Joseph Knoll, and the uses of the medicine. It explained basically everything I spent hours researching on in a single report which I have printed out and am bringing to my visit next week. It talks about it's unique selective MAO-B inhibiting properties, catecholamine activity enhancing ability, neuroprotection from various neurotoxins, anti-aging possibilities, and most importantly its effectiveness in teating depression.
I brought it up the last time I met with the doctor but he said that, to his knowledge, it didn't work very well with depression and that he'd never heard of it used for this in quite some time and was mainly used as a medicine for Parkinsons and that it wasn't the best choice, in his opinion. Knowing as much as I know now, I believe he is unaware of some of deprenyl (selegiline HCL - Eldepryl in the US)'s potential benefits and recent findings. Who could blame him? He deals with psychotropic drugs that deal with depression and few doctors use deprenyl for this purpose. All that he knew was that at MAO-B selective doses (above 15mg, it becomes a full MAOI) it was not SOLELY effective at treating depression. My paper describes the studies that were done on atypical depressives, tretment-resistant depressives, and major despressives, and that effective treatment levels required dosages in the 20-30, even 60mg range. Well above MAO-B selective doses. Even though the treatments were effective and had low side-effects, there are risks involved with all-out MAOI's like diet restrictions (such as the "cheese effect"). So I can see where he's coming from in this light. But, there were three studies that suggested effective antidepressant action at selective MAO-B inhibiting doses.
That study was just the beginning of the paper's deprenyl-depression studies. What's eye-catching is what followed: "In 1978 Mendelwicz and Youdim treated 14 depressed patients with low-dose deprenyl (< or =10mg) plus 300mg 5-HTP 3 times daily for 32 days. Deprenyl potentiated the antidepressant effect of 5-HTP in 10/14 patients. 5-HTP enhances brain serotonin metabolism, which is frequently a problem in depression, while deprenyl enhances dopamine/noradrenalin activity" (how? - I'll explain in a bit). "Under activity of brain dopamine, noradrenalin (norepinephrine), and serototin neural systems are the most frequently cited biochemical causes of depression. So, deprenyl plus 5-HTP would seem a natural antidepressant combination."
The next one gets even more promising! "In 1984 Birkmayer, Knoll, and colleagues published their successful results in 155 unipolar depressed patients who were extremely treatment-resistant. Patients were given 5-10mg deprenyl plus 250mg phenylalanine daily. Approximately 70% of their patients achieved full remission, typically within 1-3 weeks. Some patients were continued up to 2 years on treatment without loss of antidepressant action. The combination of deprenyl plus phenylalanine enhances brain PEA activity, while both deprenyl and PEA enhance brain catecholamine activity. Thus deprenyl plus phenylalanine is also a natural antidepressant combination."
Almost equally impressive: "In 1991 H. Sabelli reported successful results treating 10 drug-resistant major depressive disorder patients. Sabelli used 5mg deprenyl daily along with 100mg vitamin B6, and 1-3 grams phenylalanine twice daily as treatment. 6 of 10 patients viewed their depressive episodes terminated within 2-3 days! Global Assessment Scale scores confirmed the patients' subjective experiences. Vitamin B6 activates the enzyme that converts phenylalanine to PEA, so the combination of the three is a bio-logical way to enhance both PEA and catecholamine brain function, and thus to diminish depression."
Here is why the catecholamine enhancement is so important in treating depression, especially in those whose depression can be related directly to dopamine under-activity (as in my case). You see, even if deprenyl's oringinally hypothesized mode of action - directly increasing synaptic dopamine levels through MAO-B inhibition - is false, deprenyl's MAO-B inhibition still provides part of its benefit.
It wasn't until the 1990s that Knoll's deprenyl research took a new direction. Working with rat brain stems, rabbit pulmonary and ear arteries, frog hearts and rats in shuttle boxes, Knoll discovered a new mode of action of deprenyl that he believes explains its widespread clinical utility. Knoll discovered that deprenyl [selegiline] (and it's cousin, PEA) are "catecholamine enhancers". Catecholamines refers to the inter-related neurotransmitters dopamine, noradrenaline, and adrenaline. Catecholamines are the transmitters for key activating brain circuits - the mesolimbic-cortical circuit and the locus coeruleus. The neurons from these two brain circuits project from the brain stem, through the mid-brain, to the cerebral cortex. They help to maintain focus, concentration, alertness and effortful attention. One of the reasons the doctor put me on Adderall! - but it seems obvious Adderall is only a temporary fix as it is well documented that the human body develops tolerance (whether it's 6 days or 2 years, everyone's different) to amphetamines, including d-amphetamine, quite quickly. Plus, amphetamines are known to damage dopamine cells but whether or not the damage is done at clincally prescribed doses is not yet known and that scares me especially after long term use AND from what I hear, discontinuing use just sends the person right back into the hole it once lifted them out of). Deprenyl would seem much better (it even protects your dopamine cells from damage/neurotoxicity) :) Dopamine is also the transmitter for a brainstem circuit - the nigrostriatal tract - which connects the the substantia nigra (which deprenyl enhances) and the striatum, a nerve tract that helps control bodily movement.
Here's how it works: when an electrical impulse travels down the length of a neuron - from the recieving dendrite, through the cell body, and down the transmitting axon - it triggers the release of packets of nerotransmitters into the synaptic gap. These transmitters hook onto receptors of the next neuron, triggering an electrical impulse which then travels down that neuron , causing yet another transmitter release. What Knoll and colleagues discovered through their highly technical experiments is that deprenyl and PEA act to more efficiently couple the release of neurotransmitters to the electrical impulse that triggers their release. In other words, deprenyl (and PEA) cause a larger release of transmitters in response to a given electrical impulse. It's like "turning up the volume" on catecholamine nerve cell activity. And this may be clinically very useful in depression where there may be under-activity of both dopamine and noradrenalin neurons. And the key here is the addition of the supplement phenylalanine to the deprenyl to help significantly increase PEA levels (one need only look to the results of the above studies to come to that conclusion). Even deprenyl in itself has shown in autopsy studies to not only increase dopamine levels by 40-70% in Parkinson patients but increase PEA levels 1300-3500%! You see, PEA is the preferred substrate for MAO-B, the MAO that deprenyl inhibits. PEA has an extremely rapid turnover due to its rapid and continuous breakdown by MAO-B. Thus deprenyl's catecholamine activity enhancer has a dual mode of action. At MAO-B inhibiting doses, deprenyl has a huge catecholamine enhancing effects due to the major increases in PEA levels. Many authors have pointed out the probable dopamine neuron activity enhancing effect of PEA in Parkinson patients taking deprenyl. Knoll's discovery of PEA's catecholamine activity enhancer effect now explains this PEA dopamine-enhancing effect.
So my proposal on Wednesday will be to take 10mg a day of selegiline, 600mg of phenylalanine supplement, as well as a good amount of vitamin's C and E, and 1000mg of NAC. The reason for the latter is that deprenyl increases only 2 of the 3 main antioxidants made in the brain. SOD, and catalase to a lesser extent. But the third, glutathione isn't raised at all so it is recommended by Knoll that one take around 1000mg NAC (which increases glutathione levels) to normalize these levels. Good amounts of vitamin C and E help very much as antioxidants themselves. I will ask to discontinue Adderall and taper off the Wellbutrin as well. Wellbutrin is now said to be mainly a noradrenalin reputake inhibitor while only mildly binding to the dopamine uptake sites and actually decreasing the amount of dopamine that is manufactured! I believe that Eldepryl and around 600mg/day of phenylalaine will take care of the noradrenalin AND dopamine especially."
This is why I preach so much about selegiline AND phenylalanine as the cure for depression that so many people don't know about and are missing out on. Just look at the people who have posted on the forum with positive results. I don't see how it could do anything bad other than "over-activate" those who's problems lie else where. Those that don't have MAJOR DEPRESSION I think will almost definately benefit, especially with Klonopin for those who can't get to sleep. -Jason911
poster:Jason911
thread:96388
URL: http://www.dr-bob.org/babble/20020301/msgs/96388.html