78 replies to this topic

[SpawnMoreOverlords]

Is Rasagiline really that expensive ? quick google shows 50mg/$49 and the amounts of it taken are less than selegiline, no ?

[spermidine]

^ yeh from what i read, a dose of 1 mg rasagiline is equal or even more active than a dose of 7 mg selegiline. but who knows...

[medievil]

has rasagiline been studied in parkinson, as amphetamine's even with da depletion dramatically improve parkinson symptions wich synergizes with ldopa, its independant of da release, mdma and other deratives all do that. wont be suprised selegiline works better for acute improvements.

[spermidine]

medievil, scroll, i think it was either in this thread or the deprenyl one that i posted ncbi article comparing selegiline and rasagiline in parkinson's patients and it said switch to rasagiline dramatically improved, specifically motor function, without the side effects of insomnia and other problematics selegiline had. so yeh, it works, if not better.

[anagram]

Selegiline has a huge problem with it.. Selegiline's irreversible inhibition of MAO-B and MAO-A are not the only enzymes it binds to. Selegiline covalently attaches to and inhibits CYP enzymes and a probable slew of other proteins structures.
http://www.ncbi.nlm....pubmed/22936314

Not only does this effect probably drives some of the toxicity of Selegiline, but the fact that at higher doses Selegiline unselectively inhibits MAO-A is a big no, no. Selegiline can potentially cause hypertension because of MAOA inhibition, something which has pro aging implications. In addition to this side effect, inhibition of MAO-A prevents the induction of anti apoptic proteins, meaning that the less selective higher dose of Selegiline has the possibility of promoting cell death because it makes unavailable the anti apoptic proteins which are neuroprotective.
http://www.ncbi.nlm....pubmed/22968599
http://www.ncbi.nlm....pubmed/23231395


Rasagiline, the safer alternative to Selegiline, will primarily inhibit only MAO-B, thus promoting the neurorestorative and health benefits of MAO inhibition but without the (amphetamine-toxic- ) and potentially life threatening side effects that Selegiline produces in some circumstances.

If you are going to use Selegiline, take a 6mg EMSAM patch or cut one in half. Currently, the new Rasagiline drug is un obtaninable for those who are concerned with budget, this does not mean you should settle for the potentially toxic tablet form of Selegiline and suffer the risk of reduced life span.

[RS3RS]

Not only does this effect probably drives some of the toxicity of Selegiline, but the fact that at higher doses Selegiline unselectively inhibits MAO-A is a big no, no. Selegiline can potentially cause hypertension because of MAOA inhibition, something which has pro aging implications. In addition to this side effect, inhibition of MAO-A prevents the induction of anti apoptic proteins, meaning that the less selective higher dose of Selegiline has the possibility of promoting cell death because it makes unavailable the anti apoptic proteins which are neuroprotective.
http://www.ncbi.nlm....pubmed/22968599
http://www.ncbi.nlm....pubmed/23231395

How does this conclude anything other than the already accepted advice of "don't take high doses of Selegiline", though? Neuroprotective doses are already extremely below the MAO-A inhibition range, unless I'm missing something. Good points on the rest of the post though!

[anagram]

you are definitely right, MAO-B inhibition occurs at a lower dose of Selegiline. Most MAO inhibitors work in a dose dependent manner, which means that MAO-B inhibiting doses also involve inhibition of a portion of MAO-A, it is just a very miniscule amount of MAO-A inhibition. However, any MAO-A Inhibition is less than acceptable in any circumstance, whether you are attempting to increase your life span or cure Parkinsons. Real trouble comes in to play when you are treating Parkinsons patients with >10mgs, its moderately more toxic in these amounts, some studies have shown higher dose's to do damage.

What's germane is that sodium butyrate, phenyl butyrate, and butyric acid all have neuroprotective mechanisms against MPTP induced dopaminergeic loss.
http://www.ncbi.nlm....pubmed/22723850
http://www.ncbi.nlm....les/PMC3189510/

This begs the question... what exactly when you inhibit MAO-B, which subsequently provides protection against MPTP? I believe that when dopamine is not metabolized by MAO, it is turned into various tyrosols and catchols which then activate the same protective switch that is activated by benzoic acid. Perhaps the reason why neurons live so much longer than other cells in the body is because they're HDA(histone de acetylase) is constantly being inhibited by neurotransmitters and degradation products.

[jadamgo]

This begs the question... what exactly when you inhibit MAO-B, which subsequently provides protection against MPTP? I believe that when dopamine is not metabolized by MAO, it is turned into various tyrosols and catchols which then activate the same protective switch that is activated by benzoic acid. Perhaps the reason why neurons live so much longer than other cells in the body is because they're HDA(histone de acetylase) is constantly being inhibited by neurotransmitters and degradation products.

Also, the reduction in DOPAC concentrations from decreased MAO-B activity protect the cell from oxidative damage, and the reduction of ammonium ions has its own benefits too.

I'd be cautious about giving one reason neurons live so long -- they're programmed to do so, probably by a wide variety of mechanisms. Let's not forget the fact that they're surrounded by multiple classes of glial cells, whose primary purpose is to protect and nourish neurons.

I am thinking about using selegiline at moderately high doses(15-30), sublingually as a non-selective MAOI, since Parnate seems to be extremely effective in social anxiety (and I am hoping it will be effective for AvPD/SPD related symptoms as well, since those are really the root of my social problem right now). I just need to read up more on diet limitations just to be safe, and my selegiline needs to hurry up and get here. Maybe not though, considering the looks of the increased mortality with a high dosage. Parnate itself would probably be better for that purpose. AMPH or other stimulants would probably be ideal for the entirty of my problems, but I can't currently get my hands on any.

Sublingual doses are far lower than oral doses. Doses of 20-50mg have been used orally for MDD and related conditions with MAOI response, but that treatment is obsolete. I'm not sure I'm prepped to weigh in on the discussion as to whether or not full MAO inhibition is a good thing, but I will say this -- if you want to use sublingual selegiline for psychiatric purposes, 5-10mg per day will do ya. As for parnate, its side effects tend to be worse, but there's little doubt as to its effectiveness as a dual MAOI/catecholamine releaser.

Oh, and usually MAOI treatment decreases blood pressure over the long term due to norepinephrine depletion in the sympathetic nervous system. It seems that trace amines like octopamine fill peripheral adrenergic neuronal vesicles, displacing norepinephrine. As these trace amines tend to be more selective for beta-adrenergic receptors than alpha-adrenergic receptors (unlike NE), a mild widespread vasodilation sets in throughout the body, with an accompanying mild increase in cardiac output.

[spermidine]

btw this might seem like a troll question but; can you absorb selegiline rectally ? i know its not usually discussed we consume any substance in such vile way but from my experiences it works really fast and its pretty potent in effect. can selegiline be absorbed better like this and without the nasty amphetamine metabolites circulating in your body ?

[capob]

Just curious, but wouldn't an increased amount of dopamine owing to MAO-B inhibition potentially both decrease the number of receptor sites and the amount of produced dopamine, neutralizing the effect of deprenyl?

[spermidine]

^ good question im curious too

[medievil]

Just curious, but wouldn't an increased amount of dopamine owing to MAO-B inhibition potentially both decrease the number of receptor sites and the amount of produced dopamine, neutralizing the effect of deprenyl?

Id imagine it needs a tolerance reducer like memantine.

[fntms]

Currently, the new Rasagiline drug is un obtaninable for those who are concerned with budget, this does not mean you should settle for the potentially toxic tablet form of Selegiline and suffer the risk of reduced life span.

I got cheap generic Rasagiline from alldaychemist. Worked well, but you get a tiny pill which still needs to be cut in 4: I read that the 2mg rasa pill = 10mg selegiline, so you need to adjust from there...

Stopped taking it a month ago because even minuscule amounts caused some scary orthostatic hypotension/heart flutter issues...

Miss the verbal fluency though...

[renfr]

Orthostatic hypotension? With how much mg?
Problem is that you can't take it for prolonged periods of time, MAO inhibition being irreversible it accumulates overtime and ends up being dangerous.
Did it occur during the first week or after several weeks of continuous use?

[fntms]

To be honest I didn't actually measure the drop in tension, which seemed mostly transient and was "felt" (lightheaded, missing heart beats...) and always happened when I would lie or sit down etc... (I must also add that I was taking andrographis that also has a hypotensive effect apparently...)

I had a scary episode when I had continuous (painless) heart flutter lasting the whole night...that was after about two months of minimal selegiline use (maybe 1.25mg every other day max) then I stopped selegiline for a few weeks then took rasagiline for about one month also at very low dose (difficult to measure as it was just a tiny fraction of a tiny pill) but which felt like more than the 1.25mg selegiline).
As the flutter and mild hypotension were still happening I just quit.

I'd say the first two months were fine but then the problems arose...
I have stopped for one month now and still get the occasional flutter, but much milder than before...I still feel there is some kind of MAO inhibition going on: stims like coffee and green tea still feel better than before! I hope it all normalizes soon...

[KoolK3n]

This begs the question... what exactly when you inhibit MAO-B, which subsequently provides protection against MPTP? I believe that when dopamine is not metabolized by MAO, it is turned into various tyrosols and catchols which then activate the same protective switch that is activated by benzoic acid. Perhaps the reason why neurons live so much longer than other cells in the body is because they're HDA(histone de acetylase) is constantly being inhibited by neurotransmitters and degradation products.

I cannot speak for all the MAO-B inhibitors but Deprenyl maybe preventing neurotoxicity of MPTP by upregulating Nrf2! Nrf2 is a critical gene for life extension purposes. It's protective because it enhances the body's natural antioxidant defense system.
http://www.ncbi.nlm....pubmed/22019741
http://www.ncbi.nlm....pubmed/16325767

More on Nrf2:
http://www.anti-agin...rmetic-effects/

Edited by KoolK3n, 09 April 2013 - 06:48 PM.

[**DEACTIVATED**]

Just curious, but wouldn't an increased amount of dopamine owing to MAO-B inhibition potentially both decrease the number of receptor sites and the amount of produced dopamine, neutralizing the effect of deprenyl?

^ good question im curious too

Just curious, but wouldn't an increased amount of dopamine owing to MAO-B inhibition potentially both decrease the number of receptor sites and the amount of produced dopamine, neutralizing the effect of deprenyl?

Id imagine it needs a tolerance reducer like memantine.

No, not according to this: http://www.longecity...ving-tolerance/

I started this thread basically asking the same question. Apparently that's not how it works with MAOBI. Maybe it's possible with very high doses though..

[KoolK3n]

No, not according to this: http://www.longecity...ving-tolerance/

I started this thread basically asking the same question. Apparently that's not how it works with MAOBI. Maybe it's possible with very high doses though..

There is some physiological adaptation though with dopamine synthesis from tyrosine hydroxylase
http://www.ncbi.nlm....1350320/related

I don't think this has a significant impact on the overall effect of deprenyl anyway. Interesting thing, the part of the brain responsible for producing most of the brains dopamine, the substantia nigra is protected from age related degradation by deprenyl!!
http://www.ncbi.nlm....pubmed/8732287/
http://www.ncbi.nlm....ubmed/10343976/

Crackalackn I noticed in the link you provided you were concerned about D2 downregulation. D2 activation actually reduces dopamine in the synaptic cleft because it increases DAT. If you're concerned about downregulation of D2, look into Inositol. It upregulates D2.

Edited by KoolK3n, 10 April 2013 - 02:16 PM.

[KoolK3n]

Oops I meant to use this too
http://scholar.googl...ved=0CCgQgQMwAA

[KoolK3n]

The reason for the reduction in dopamine synthesis from deprenyl maybe from the spillover effect. Gradually inhibiting MAO-A seems to induce this adaptation but not when only MAO-B is inhibited from initial deprenyl treatment.
http://onlinelibrary...enticated=false

Alcohol upregulates MAO-A and a metabolite (5HIAA) that chronic Deprenyl reduces. Of course alcohol is very unselective in its overall effects.
http://www.ncbi.nlm....ubmed/19572987/

In theory, combining Deprenyl with a little beer should keep tolerance levels somewhat down but like always nothing ever goes according to plan lol.

Edited by KoolK3n, 10 April 2013 - 04:04 PM.

[**DEACTIVATED**]

KoolK3n,

Thanks for enlightening the subject a bit more. Do you have any dosage recommendation for Inositol? Personally I don't like mega-dosing anything.

If Deprenyl is dosed low enough (2mg/day) then there shouldn't be any issues, right? You mentioned the spillover effect which shouldn't be reached at low doses so that covers the decrease in synthesis of tyrosine hydroxylase.

I'm a bit confused how alcohol can help. Are you saying that alcohol will upregulate the metabolite 5HIAA to compensate for Deprenyl reducing it? I still drink beer and alcohol occasionally, whatever it's worth, while using 2mg/day Deprenyl.

[KoolK3n]

KoolK3n,

Thanks for enlightening the subject a bit more. Do you have any dosage recommendation for Inositol? Personally I don't like mega-dosing anything.

I don't know the optimal dosage sorry. I hate mega dosing anything too but many people have reported positive effects over 5-20 grams daily.

[KoolK3n]

If Deprenyl is dosed low enough (2mg/day) then there shouldn't be any issues, right? You mentioned the spillover effect which shouldn't be reached at low doses so that covers the decrease in synthesis of tyrosine hydroxylase.

I'm a bit confused how alcohol can help. Are you saying that alcohol will upregulate the metabolite 5HIAA to compensate for Deprenyl reducing it? I still drink beer and alcohol occasionally, whatever it's worth, while using 2mg/day Deprenyl.

Maybe...I know MAO-A inhibition starts gradually when MAO-B is just about completely inhibited over time. To prevent this from happening, beer is one method because of the up regulation.
This can't be the case though because then chronic Emsam patients wouldn't be able to eat tryamine rich foods for instance. I need to do more research at home as I've been posting on my iPhone all day.

Edited by KoolK3n, 10 April 2013 - 06:06 PM.

[brainslugged]

Do you have any dosage recommendation for Inositol? Personally I don't like mega-dosing anything.

I tried inositol and my younger brother is currently taking it (his for OCD).

I took 2g/day and planned to work up to 16g-18g/day, which is the maximum, but you really have to start low, and very few people actually have to reach the higher range. I got some pretty bad effects from just the 2 or 3 grams I was taking. My brother has so far been barely affected. It slightly reduces rituals, but I don't know if it is just a bias or something. He is at 2g, and she says that it is helping him, but I don't see a major improvement. She doesn't want to go any higher, though, which is understandable.

This isn't an official study, but it is a good article on the topic.

[KoolK3n]

Ok...am finding several conflicting studies. My post tomorrow will most likely contradict what this post will contain....screw it I'm just finding more and more contradictions. What I can definitively say is since MAO-A primarily metabolizes serotonin. It can be safely combined with an SSRI as long as Deprenyl's spillover effect is limited to a pulp. Yes yes SSRIs get bad rep here but it could synergize with Deprenyl. One of the benefits of inhibiting MAO-A is the upregulation of nacetylserotonin (potent natural nootropic). This effect is seen with SSRIs too and seem safer than inhibiting MAO-A. But taking both means guaranteed serotonin syndrome. So basically you have to pick one in order to increase NAS (nacetylserotonin). As long as MAO-A is fully uninhibited, there shouldn't be any problems. That means "we" need to prevent Deprenyl from potentially interfering. This is why I proposed beer (low alcohol content to avoid dramatic interaction with GABA). Many people on depression forums are currently on Emsam and some kind of SSRI without any issue.

Edited by KoolK3n, 10 April 2013 - 11:19 PM.

[KoolK3n]

Regarding TH (tyrosine hydroxylase), its decreased activity may be somewhat avoided by coadministration of N AcetylCysteine and Forskolin. I'm uncertain with either being effective but that's all I got.

[KoolK3n]

I've made conclusion (kinda unrelated) but could be helpful later on. Reuptake inhibition of any neurotransmitter means severe downregulation of transporter expression whether its with SSRIs downregging SERT or methylphenidate downregging DAT. This idea goes completely against what you'd expect to see since the cell would've wanted those extra neurotransmitters gone. This rule does not apply to MAOIs and releasing agents. What does this mean? Well it means that if you're on an SSRI and DRI (Dopamine reuptake inhibitor), your response to other drugs such as amphetamine (Adderall, vyvanse, desoxyn), meth, and mdma will be in theory be much much weaker since it relies on a lot of DAT, SERT, etc for reversal. Maybe that's why people with depression respond better to illicit drugs because of excessive transporters just waiting to be reversed.

Edited by KoolK3n, 11 April 2013 - 01:04 AM.

[**DEACTIVATED**]

KoolK3n,

You've been down voted repeatedly in this thread.. 4 posts to be exact.

Any reason why?

Edited by CrackaLackN, 11 April 2013 - 01:25 AM.

[KoolK3n]

KoolK3n,

You've been down voted repeatedly in this thread.. 4 posts to be exact.

Any reason why?

Idk...could be the same person. I'll update this thread more tomorrow.

[**DEACTIVATED**]

I guess I deserved one too?

Well whoever you are, I don't care. All you're doing is impeding the enrichment of this forum.

At least step forward and man up so we can work together instead of silently taking action.