10 replies to this topic

[hondoleroy]

First of all, I'm quite a "rookie" to all of this. And my "life extension" concerns are of a more immediate nature than just theoretical....

I am currently combating a problem of high cortisol (over 2 x maximum normal range... as recently as Swe[tember was 4 - 6 times that maximum normal range) along with anxiety and depression. Have been taking Phosphatidyl serine, Gingko Biloba, and Holy Basil so far for the anti-cortisol effects (plus plan on adding in Magnolia Bark extract, 7-Keto DHEA, and whatever else I can find through research) to work on the high cortisol. Unfortunately no good pharmaceutical meds for lowering cortisol that don't have some major serious side effects.

My pscyh doc has had me on Ativan for anxiety since mid September and recently switched that to Xanax XR and now plans on adding an anti-depressant (to "balance out" the anti-anxiety as it seems to increase the depression effects), a new drug called Cymbalta. I know very little about the Cymbalta. This is a quote from the manufacturer:

QUOTE: Cymbalta is believed to affect the levels of two key neurotransmitters involved in depression -- serotonin and norepinephrine -- both implicated in the complex spectrum of major depression symptoms. Prozac® and many other common antidepressants, in contrast, affect only serotonin. END QUOTE

From a UK source:

QUOTE: It is possible that duloxetine (Cymbalta), due to be FDA-licensed in 2005, and milnacipran (Ixel), available in Europe, may be more effective than venlafaxine for a segment of the population that can benefit from dual serotonin-noradrenaline reuptake inhibition. Pain-ridden and melancholic depressives in particular may respond well to this class of drug. Once again, dopaminergic augmentation may be beneficial for the naturally lethargic. Unlike venlafaxine, duloxetine exerts its more balanced serotonin and noradrenaline reuptake inhibition throughout the dosage range. Duloxetine also weakly inhibits the reuptake of dopamine, and shows minimal affinity for the histamine and cholinergic muscarinic receptors. END QUOTE

Anyway, I have come across much interesting information about Deprenyl (aka Selegiline) in the treatment of depression. Specifically in regards to the use of low-dose Deprenyl along with

http://www.biogenesi...pi-deprenyl.asp

QUOTE: Similarly, Birkmayer et al. reported benefit in an uncontrolled study in 102 outpatients and 53 inpatients with unipolar depression who received selegiline hydrochloride 5 to 10 mg daily in association with phenylalanine 250 mg daily- about 70% of these patients, in whom conventional antidepressants were not effective, were reported as having complete remission. END QUOTE

Seventy percent success rate is really great when compared to most ADs!

http://www.antiaging...ract/depren.htm

QUOTE: In 1984 Birkmayer, Knoll and colleagues published their successful results in 155 unipolar depressed patients who were extremely treatment-resistant. (8) Patients were given 5-10 mg DPR plus 250 mg 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 DPR plus phenylalanine enhances brain PEA activity, while both DPR and PEA enhance brain catecholamine activity. Thus DPR plus phenylalanine is also a natural antidepressant combination.

In 1991 H. Sabelli reported successful results treating 6 of 10 drug-resistant major depressive disorder patients. (9) Sabelli used 5 mg DPR daily, 100 mg vitamin B6 daily, 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 low-dose DPR, B6, and phenylalanine is a bio-logical way to enhance both PEA and catecholamine brain function, and thus to diminish depression. END QUOTE

http://www.dr-bob.or...sgs/138787.html
http://www.dr-bob.or...sgs/430786.html


Questions

1. How is the track record of Deprenyl? Are there many problems with side effects? Any precautions that should be specifically noted? Any problems with taking Deprenyl with Xanax (Drug Digest reports NO drug interactions between the two)?

2. How does one go about obtaining Deprenyl? As it seems to be approved basically for Parkinson's Disease, I have concerns that my psych doc will prescribe this. Is there any other way that it can be obtained? Some place like International Antiaging Systems possibly? Is a perscription necessary in those cases?

3. Does anyone have any additional links to info on Deprenyl, specifically as may concern its ability to counter depression?

Thanks in advance.

[vortexentity]

Deprenyl increases the availability of dopamine by acting as a selective MAO-B inhibitor and has an aphrodisiac effect for some. I happen to know some old farts that swear by it. The increased dopamine sure makes people more sexually active. Increased dopamine is of course the reason as this is the bodies main reward chemical.

Along with endorphins of course.

Add some L-tyrosine about 300mg per day and about 200mg of D,L-Phenylalanine and about 50mg of 5-HTP and you have a combo for reducing stress and depression that is pretty hard to beat. It will also act a lot faster than most persrciption depression drugs.

It might be too much for some but I have tried this stack and It has some amazing effects. I know some 70 something old men that take this and have the biggest smile of their face they have had in many years.

If deprenyl is not available to you try SAM-e and or NADH as they both work to naturally optimise dopamine and serotonin levels.

Web References:
http://www.immunesup...ws/99spr006.htm
http://www.smart-dru...ession-SAMe.htm

[hondoleroy]

Thanks for the info.

I noticed that a number of postings indicated the presence of Deprenyl in their "stacks" and wondered if this was something that had to be obtained stricty via local prescription (which my psych doc may or may not do.... she's usually pretty liberal with a lot of that type of stuff), or if it can be obtained via offshore avenues....

[vortexentity]

Offshore is cheaper and no hassle. PM me for detail of low cost sources.

One precaution is that it can upset your stomach. Some get heartburn and it goes away when they quit taking it for a while. Other than that it is well tolerated by most people.

Edited by vortexentity, 15 January 2005 - 03:05 AM.

[hondoleroy]

RE your mentioned stack....

QUOTE: Add some L-tyrosine about 300mg per day and about 200mg of D,L-Phenylalanine and about 50mg of 5-HTP and you have a combo for reducing stress and depression that is pretty hard to beat. It will also act a lot faster than most persrciption depression drugs. END QUOTE

Is that with 5mg Deprenyl or 10 mg? And if 10mg, do you take 5 mg once a day or twice a day?

I read similar stack info frim user on another site that had user taking 5mg Deprenyl in AM with 250 mg DLPA (DLPA before brekfast on empty stomach and Deprenyl with breakfast drink), then took 5 mg deprenyl with lunch and tyrosine in midafternoon (on empty stomach) and took the 5-HTP (along with Melatonin) just before bed.

Better that way or take whole daily dose of deprenyl n AM at once?

Also, I am on low dose Xanax XR for background anxiety problems. Any chance (strong chance!) that this combo would agitate anxiety more? I am hoping to get depression / lack of motivation / fatigue taken care of with this combo and then wean off Xanax XR and replace with something else (SJW possibly? Picamilon possibly?)....

Leroy

[stellar]

I want to try Deprenyl, is it ok if you're under 30? Do you buy the tabs or the liquid version?

[lynx]

Liquid is inherently easier to do low dosing for young people.

[johnmk]

Do we metabolize it differently if we ingest it through our oral cavity membranes, rather than through the stomach? I've heard this may be the case, but would appreciate some of your opinions.

[johnmk]

Liquid is inherently easier to do low dosing for young people.

I can readily admit that. Is it necessary or optimal in your opinion to dose daily? I read that some of the effects (at least MAOI-B) are long-lasting, i.e. weeks. Do you believe and/or does research show that the neuroprotective effects are maintained as well if for instance you were to dose 5mg every other, or every third day?

-John

[johnmk]

This website:

http://brain.hastypa...php/t-2441.html

Raises some concerns regarding pyridoxal kinase.

The reuptake inhibitors tend to increase the levels of dopamine, serotonin, and norepinephrine over time. When these medications create an excess of the neurotransmitter, relative to the neurotransmitter receptor, then the excess neurotransmitters block the action of a key protein, pyridoxal kinase, which activates B6 by adding a phosphate group as this vitamin is entering the cell. Once pyridoxal kinase is inhibited on the inside of the cell, it doesn't matter how much vitamin B6 a person takes, the cell will still act like it is B6-deficient, because the B6 can't be activated. This type of reaction will only happen in those cells, such as specific regions of the brain, in which the neurotransmitter is in excess, due to a medication. This is a general mechanism, applicable to all individuals who take a re-uptake medication, but whose dose is not adjusted continuously to take into account the changes that occur over time (embedded membrane receptors become less embedded and more active). The body essentially decides that it has too much of the neurotransmitter, relative to the exposed neurotransmitter receptor, and decides it is time to cut back on the production of the neurotransmitter. One way for the body to turn of neurotransmitter production is to turn off the activation of B6 which is essential to producing serotonin, dopamine, norepinephrine, and many other neurotransmitters that control mood and behavior.
The problem with all of this is that each medication usually affects one neurotransmitter. For example, ritalin is a dopamine re-uptake inhibitor. If dopamine becomes in excess of the dopamine receptors, dopamine inhibits pyridoxal kinase and blocks B6 activation. Unfortunately, blocking B6 activation also blocks the production of serotonin, as a side effect, where in fact serotonin was probably at proper levels originally. This is what causes an adverse side effect. Lower serotonin levels can lead to one form of depression, or loss of appetite. Both of these symptoms are very, very common side effects of ritalin, so the way physicians handle it, is to give a serotonin re-uptake inhibitor. This may correct a few of the serotonin deficiency symptoms for awhile, until the SSRI also contributes to a growing B6 deficiency by inactivating pyridoxal kinase. Then a new symtpom appears - sexual dysfunction, strong suicidal tendencies, tardive dyskinesia, tardive akathesia, etc. and with each new symptom, a new medication is usually prescribed. Some children end up on as many as 5 or 6 psychotropic medications, all causing new symptoms over time. There is no doubt in my mind that many of the medications can help problems, but unless the medication is continously adjusted for weight/receptor exposure (hard to do), a medication which seemed fine initially and for even a few years, can turn into a nightmare eventually. This requires very close monitoring by a very good physician. Of course the problems are compounded for a subset of children who metabolize medications poorly, have allergies, pyroluria, or intestinal infections, but it nevertheless happens in all individuals to some degree. All of this is in the medical/scientific literature. It is just that physicians don't have enough time to keep up with the literature.

To compound the problems even more, when a person becomes B6 deficient, it affects heme production and the subsequent activation/production of cytochrome P450s, the proteins which clear medications and toxins. Thus the individual becomes alot more sensitive to foreign substances, foods, toxins, medications over time. This is a continuing problem for getting the medication dosage correct. The dose that was once working, begins to become toxic because it is not being cleared as quickly as it once was in the body. Thus, adverse symptoms can appear, even after years of the same medication, because of ongoing changes in the body.

SSRIs can cause movement disorders... Parkinsonian type movements, tremors or facial/mouth/tongue ticcing in about 25% of long time users.

SSRIs can also interact with over the counter cough/cold remedies containing DM (dextromethorphan). It is not recommended to take DM containing products with SSRIs because of the risk of serotonin syndrome. This warning has not made it to the packaging of the products yet (they only list a warning for MAOI's at this time). http://archfami.ama-...ent/full/7/1/78

What are the implications for long-term use of methylphenidate (Ritalin), dextroamphetamine (Dexedrine) or mixed amphetamine salts (Adderall), and more importantly selegiline (a.k.a. deprenyl / l-deprenyl), with regard to the above information (which seems to make sense, I just lack the context and knowledge to know if it's true, true to a variable or fixed degree, or completely untrue, etc.). My intention is to use selegiline at a dosage that works optimally for me without side-effect (or even side-effect potential, preferably), and also to complement with amphetamine or methylphenidate.

You may wish to refer to my thread here, if you're interested in helping me or want some links to good information regarding cerebral cortex dopamine levels. Enjoy!

http://www.imminst.o...f=169&t=5826&s=

-John

[philmicans]

Deprenyl is a non-reversible inhibitor of MAO-B and according to Professor Jozeph Knoll (the pharmacologist who invented seligiline- the other name for Deprenyl- in the 1960's), he stated to me that to return to "normal" (i.e. biological) levels of MAO-B takes a period of 3-weeks of abstinence. In other words if you have been on Deprenyl for some time it will take a period of 21-days to return to your "normal" levels, this of course may not be a good thing as "normal" is not necessarily "optimal" as demanded in antiaging medicine.
However, Dr. Knoll now believes that the effects of Deprenyl are far more to do with its enhancement of PEA and that these enhancer effects are more likely responsible for its benefits. To read his technical article go to: http://www.antiaging...ylmechanism.htm to read another excellent (but not so technical article) by biochemist James South go to: http://www.antiaging...ract/depren.htm
Naturally these substances are available from www.antiaging-systems.com in liquid and tablet forms, no prescription required although a signed declaration of responsibility is.
Lastly, Dr. Knoll does have an excellent book out called "The brain and its self" published by Springer. It's a conglomeration of his work and his thoughts on the neurochemical concept of the innate and acquired drives of the brain- I highly recommend it.
Also, very recently, a new drug called Rasagiline (Azilect) has been approved in parts of Europe. This is a highly specific MAO-B inhibitor that in this regard is believed to be 5-10 times more potent than deprenyl. If anyone is interested, some details are also available at: http://www.antiaging...a2z/azilect.htm