Selegiline (l-deprenyl) - too good to be true?

[streetsurfer]

Also an update, I stopped the ritalin/selegiline combo quite a few months ago. Gradually I built up a tolerence to it and started getting alot of side efects (like almost dieing several times).
It is fucked up because it is seriously addictive and the longer you take it, how selective it is going to be on any givin day can become unpredictable. It also fucks with your memory, I presented to ER one night thinking I was dieing then went home, forgot about the whole experiece and dosed again!!

I also alianated myself from quite a few people with my manic behaviour and managed to get myself assulted on the street.

Its bad news, don't fuck with it.

 

[Morb]

i think you can have a good time on selegiline alone, i only take in the 1.25mg/eod range and i feel heaps better, phenyalanine is a great combo if you're looking for adhd help, i'm going to take a break for a month after finals and then try the cyprenil 1mg/day (i'm almost 35, so that is right in knoll's range), at times i've felt like upping the dose because when i first started at 5mg it was like being stoned in more ways than one ie i felt great and i wasn't getting shit done, it works great for me as an antidepressant and antianxiety somehow, with the l-phen i seem to be gaining muscle mass as well, i think it has to do with decreasing my stress horomones, i can focus better and i'm not living in perpetual fight or flight mode, don't forget an antioxidant equalizing stack, and yes it's hard to get a reply on dep because molko spams every thread even when you specifically request he not do it, that's the life of an exblue i guess

 

[Morb]

molko please don't respond

FDA News
FOR IMMEDIATE RELEASE
P06-68
May 17, 2006
Media Inquiries:
Kimberly Rawlings, 301-827-6242
Consumer Inquiries:
888-INFO-FDA



FDA Approves New Treatment
for Parkinson's Disease
The Food and Drug Administration today approved Azilect (rasagiline), a new molecular entity, for the treatment of Parkinson's disease. The drug is a monoamine oxidase type--B (MAO-B) inhibitor that blocks the breakdown of dopamine, a chemical that sends information to the parts of the brain that control movement and coordination.

"This is a welcome development for the more than 50,000 Americans who are each year diagnosed with Parkinson's disease, " said Dr. Steven Galson, Director of the Center for Drug Evaluation and Research. "Parkinson's is a relentless disease with limited treatment options, and each new therapy is an important addition to the physicians' treatment options."

Parkinson's disease is a chronic, progressive neurodegenerative condition caused by the destruction of the brain cells that produce dopamine. As the level of this chemical declines, messages from the brain telling the body how and when to move are delivered more slowly, leaving a person incapable of initiating and controlling movements in a normal way.

Azilect was approved for use as an initial single drug therapy in early Parkinson's disease, and as an addition to levodopa in more advanced patients. Levodopa is a standard treatment for Parkinson's disease. The safety and effectiveness of Azilect was demonstrated in three 18- to 26-week controlled clinical trials.

One of the studies compared the effects of Azilect with the effects of placebo in 404 patients with early Parkinson's. Compared with patients on placebo, the condition of patients on Azilect showed significantly less worsening on a rating scale that measures the ability to perform mental and motor tasks as well as daily living activities.

The other two studies compared the effects of Azilect with placebo when taken together with levodopa by over 1100 patients with more advanced Parkinson's. In these studies, patients using Azilect together with levodopa had significantly less time per day with relatively poor function and mobility as compared with patients on levodopa and placebo.

Azilect may be associated with hypertensive crisis if patients also consume tyramine-rich foods, beverages (such as cheese and red wine) or dietary supplements or amines contained in many cough/cold medications. Therefore, patients will need to avoid these sources of tyramine and amines when taking Azilect. As with most other medications for Parkinson's, Azilect has the potential to cause involuntary movements (dyskinesias), hallucinations and lowered blood pressure. These side effects are described in the product labeling.

During development, melanoma was diagnosed in a small number of patients treated with Azilect. Although the FDA has concluded that the available data do not establish that Azilect is associated with an increased risk for melanoma, it appears that compared to the general population, patients with Parkinson's disease have an increased risk for this form of skin cancer. In order to address the question of whether or not Azilect itself increases such risk, the drug's manufacturer will perform a Phase 4 (postmarket) study. The product labeling will recommend that patients undergo periodic dermatologic examinations.

Azilect is manufactured by Teva Pharmaceutical Industries in Tel Aviv, Israel.








I don't see why if deprenyl/levadopa is a bad combination that rasagaline/levadopa will be any better. Didn't the former trials show all the life shortening aspects after 6mos to a year? This test was only several weeks long which was the honeymoon phase for dep/ld. But after deprenyl and now rasagaline have moved into fda territory I see tighter regs coming for any of us in the usa ordering dep without a scrip.

How is your rasagaline cycle going phase-d?

 

[phase_dancer]

Rasagiline: Too expensive for me. I'll stick to deprenyl for the present. At my current ~1.25mg/day (1/4 tablet) I feel no side effects, little synergism with caffeine, and no direct stimulation. Something is however affecting my sleep at present, but this might be caused by other things.

At this dosage, my prescribed 100/5mg tablets will last a long time, making it a very affordable noo-tropic. 5mg/day is definitely too much IMO. I have no desire whatsoever for any stimulation affects, so the bruxia and general feeling of being wired which accompanied the higher dosage were most uncomfortable.

I'll be interested to see the results of phase 4 clinical trials with Rasagiline.

 

[Morb]

I am at 1.25 eod, supplemented by 3000mg C, 900mg E, 800mg NAC and some ala. How long are you staying on? I'm in the 7-8wk range and I'm going to take some time off and contrast. I have a bottle of cyprenil in the fridge that I will definitely start by sept 1, about 3 weeks before I start orgo. I will most likely run it about 8mos since there isn't an appreciable break between semesters. I turn 35 this summer so I am going to try 1mg/d. Most things I've read say you need the daily use for a nootropic. I agree that 5mg is too much, at least for me. It fucks me up, I can't concentrate and I sleep forever, it is like being stoned. I wouldn't rule it out for your sleeplessness though. What do you think about such a long term cycle that I am proposing? And how old are you?

 

[phase_dancer]

7-8 weeks is not a bad course time, however, I did 12 weeks last time and will probably do this again as I didn't really notice the full affects until about the 6 week mark. I'm 2 weeks into this latest regimen. As for how old; I'm quite a bit past the std bluelight retirement age

 

[zorb]

Interested to hear you are feeling the effects of your prescribed selegiline, phase_dancer. I went to an excellent (non-standard-GP) doctor, and he was quite happy to write me a script for Eldepryl (the PBS brand we get here i believe) but he said that is poor quality, and quite simply "won't work". He suggested i order online

To contribute further re: my selegiline experiences, i am now 4 weeks into my course. I started on 5mg/day, with 500mg of N-Acetyl-L-Tyrosine. This was _great_ (in terms of giving me an up feeling - not helping with ADD symptoms tho), but gave me a nice case of anxiety/lo-rent mania. I dropped the Tyrosine, and have (just recently - 2 days ago) scaled back my dosage to 2.5mg/day. This seems to be a nice balancing point where my ADD symptoms are somewhat addressed and I do not feel anxious/manic at all.

Still, its weird that Deprenyl had a much greater effect (total 'zoning in' and no ADD symptoms at all) during the latter stages of my first course (where i scaled _up_ from 2.5mg/second day --> 5mg/day before i ran out).

Oh well, the process of self-experimentation continues....

 

[Morb]

7-8 weeks is not a bad course time, however, I did 12 weeks last time and will probably do this again as I didn't really notice the full affects until about the 6 week mark. I'm 2 weeks into this latest regimen. As for how old; I'm quite a bit past the std bluelight retirement age

Only reason I asked was because of Knolls age/dosage recommendation table.

 

[streetsurfer]

Anyone still on selegiline? I am looking at going on Nardil or something...fuck, the only thing that ever worked was that selegiline/rit combo but it was bad bad news

 

[hoojoo]

Just a question about selegiline, if you're taking a low daily dose (say 5mg/day), do you need to be on a maoi diet?

 

[phase_dancer]

Just a question about selegiline, if you're taking a low daily dose (say 5mg/day), do you need to be on a maoi diet?

No, not normally. Tyramine rich diets are very dangerous when MAOA inhibitors are used. Selegiline doesn't normally inhibit MAOA at lower doses, however, if high doses are used - definitely not advised - then maoi dietary planning would be a must. Care also needs to be taken if some additional medications are to be used with selegiline. Check the MIM's entry or better still, ask your GP.

 

[hoojoo]

Thanks for that phase_dancer. Another question (two actually):

1. Could you recommend any basic reading materials for someone with little knowledge about nootropics?

2. You wouldn't happen to know any easy to understand primers on psycho-pharmacology would you?

Cheers mate!

 

[phase_dancer]

^ Unfortunately the paper I posted the link to on page 8: (The therapeutic potential of monoamine oxidase inhibitors) is no longer free. It gave a good explanation of the action of MAOIs. Some found it a little too technical although most abbreviations and terms were well explained.

There's lots of online stuff out there on noo-tropics. Try starting with Erowid

 

[streetsurfer]

Well, I have decided to give selegiline another go. Nothing has really worked with my depression, I was going to go onto Nardil then I read about how psysier motherfuckers are manufacturing it now and have changed the formula and now it is nowhere near as effective.

I have read selegiline has a similar profile to nardil. Its problem being extreamly variable absorbtion in the GI tract. And seeing there is no transdermal selegilne here yet I am going to do what I did when I was abusing it with ritalin....make up gell caps full of oil and put the tablet in it. Oil increasing and making the bioavailability more consistant. It has helped me in the past, hope it will again

 

[tadfish]

not sure bout that mate

Sorry I didnt read all of the posts in the thread.
Years ago I tried DEDI Deprenyl citrate....was great for about 3 days...then I was feeling great, and obviously stupid and ate some aged cheeze....freakin reacted....was only taking like 1 mg of liquid deprenyl....hypertension..and no sleep for a week.....then went to emergency room blood pressure still like 200 over 125....

Fucked me up for a long time....I cant remember if I was also taking elavil...which now I know will cause a neuro TOXIC reaction.....

I recently tried EMSAM....if your interested you can ask me questions...but I dont think I can respond until I get about five more posts...(greenlighter)

Be really careful with Deprenyl....who ever was taking ritalin with it.....????I believe that is a NONO....

You cant take anything with it....no speed, pseudoephedrine, no DXM, no nothin....hey not even vistaril.....no opiates....

ahh well i have taken meth speed dexies and ritalin with it so..
i don't know whats wrong with u it just increases things by say 2-3 times i think. u must be talking shit or u have something wrong with u.

 

[nanobrain]

^thats a silly thing to say - selegeline is not entirely selective for B and given metabolic differences, i see no flawed logic in Eshu2012's comments, in fact, i'll heartily endorse his warning.

 

[streetsurfer]

I took selegiline one dose 1.25mg while I was a long term dexie user and it put me into instant withdrawl, suicidal, fucked up

 

[streetsurfer]

^^

I have come to have the opinion that it was more the fact that I was on effexor as well that I got such a nasty reaction as I have read it it a particually toxic combo with maois.
...stupid I know

Now however, I have been on selegiline for 4 days at 15mg per day. I am withdrawling from dexamphetamines and I can say it is nothing short of fantastic in dealing with the depression and agitation associated with doing so.

I am taking alot of benzos and propranolol also but I really belive the selegiline to be contributing.

Where I think me and other people have gone wrong with selegiline is that they have failed to reduce the does of levels build up in the body. Typically with the older maois they would administer the maxamum dose till a good responce was achieved then taper down to the minamum effective dose which was often several fold less.

Like Phase D said, I will probably reduce down to 1.25mg day as soon as I feel I have peaked in its effects this time.

But, at day 4:

Big differences I have noticed is increased sociability past what I would expect from benzos, I am usually massively socially phobic and depressed.
I changed my facial hair to a new style (long sideburns) something I almost never do and if I do I second guess it.
I feel alot more focused, my mood is great, my dreams are not bad

Of course, I have given up prozac, dexamphetamines, started living in a great share place, started vitamine e tablets and been drinking alot more alcohol so take this with a grain of salt but I do feel a centredness I have felt before on them and it is great. Shall keep you updated

 

[streetsurfer]

Deprenyl enhances the striatal neuronal damage produced by quinolinic acid

.de Pablos RM, Herrera AJ, Tomas-Camardiel M, Machado A, Cano J.
Departamento de Bioquimica, Bromatologia, Toxicologia y Medicina Legal. Facultad de Farmacia, Universidad de Sevilla, Spain. C/Prof. Garcia Gonzalez 2, 41012-Sevilla, Spain.

We have tested the effect of deprenyl on the neurotoxicity induced by the injection of quinolinic acid within the striatum. Deprenyl was unable to prevent these quinolinic acid-induced damages, but enhanced the loss of several gamma-aminobutyric acid (GABA) positive subpopulations, the loss of the astroglial population and the activation of microglia produced by quinolinic acid. These effects are produced by deprenyl potentiation of dopamine actions since dopamine depletion produced by previous injection of the dopaminergic toxin 6-hydroxydopamine within the medial forebrain bundle overcomes deprenyl effects and the involvement of dopamine in the quinolinic acid-induced toxicity in striatum. In these conditions, quinolinic acid toxic action in striatum is significantly lower and similar in the animals treated with or without deprenyl. All these data justify why deprenyl worsen some pathological signals of disorders involving excitotoxicity. This also may be involved in other secondary effects described for deprenyl.

Is that worrying? If so is this a solution and is it saying tyrosine supplimentation would help?

Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal dopaminergic neurons by endogenous kynurenic acid

.Miranda AF, Boegman RJ, Beninger RJ, Jhamandas K.
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Endogenous excitotoxins have been implicated in the degeneration of dopaminergic neurons in the substantia nigra compacta of patients with Parkinson's disease. One such agent quinolinic acid is an endogenous excitatory amino acid receptor agonist. This study examined whether an increased level of endogenous kynurenic acid, an excitatory amino acid receptor antagonist, can protect nigrostriatal dopamine neurons against quinolinic acid-induced excitotoxic damage. Nigral infusion of quinolinic acid (60 nmoles) or N-methyl-D- aspartate (15 nmoles) produced a significant depletion in striatal tyrosine hydroxylase activity, a biochemical marker for dopaminergic neurons. Three hours following the intraventricular infusion of nicotinylalanine (5.6 nmoles), an agent that inhibits kynureninase and kynurenine hydroxylase activity, when combined with kynurenine (450 mg/kg i.p.), the precursor of kynurenic acid, and probenecid (200 mg/kg i.p.), an inhibitor of organic acid transport, the kynurenic acid in the whole brain and substantia nigra was increased 3.3-fold and 1.5-fold respectively when compared to rats that received saline, probenecid and kynurenine. This elevation in endogenous kynurenic acid prevented the quinolinic acid-induced reduction in striatal tyrosine hydroxylase. However, 9 h following the administration of nicotinylalanine with kynurenine and probenecid, a time when whole brain kynurenic acid levels had decreased 12-fold, quinolinic acid injections produced a significant depletion in striatal tyrosine hydroxylase. Intranigral infusion of quinolinic acid in rats that received saline with kynurenine and probenecid resulted in a significant depletion of ipsilateral striatal tyrosine hydroxylase. Administration of nicotinylalanine in combination with kynurenine and probenecid also blocked N-methyl-D-aspartate-induced depletion of tyrosine hydroxylase. Tyrosine hydroxylase immunohistochemical assessment of the substantia nigra confirmed quinolinic acid-induced neuronal cell loss and the ability of nicotinylalanine in combination with kynurenine and probenecid to protect neurons from quinolinic acid-induced toxicity. The present study demonstrates that increases in endogenous kynurenic acid can prevent the loss of nigrostriatal dopaminergic neurons resulting from a focal infusion of quinolinic acid or N-methyl-D-aspartate. The strategy of neuronal protection by increasing the brain kynurenic acid may be useful in retarding cell loss in Parkinson's disease and other neurodegenerative diseases where excitotoxic mechanisms have been implicated.

 

[RigaCrypto]

What would be the recommended duration of a course? Has anyone noticed tolerance or withdrawal symptoms after taking it for a long time?

I've tried it just for a couple of days at 5mg/day and the effect was obvious from the first day. I felt more "awake" and focused but still with a hint of anxiety and a slight headache. I think a bit less would be ok.

As far as I know it dangerously potentiates 2C-x. Do you need to wait the full 2 weeks for MAO levels to return to normal before tripping?