How Selegiline ((-)-Deprenyl) Slows Brain Aging

How Selegiline ((-)-Deprenyl) Slows Brain Aging

Author: Joseph Knoll*

160 pages

*Joseph Knoll created Deprenyl/Selegiline in the 1960s,

How-Selegiline-Deprenyl-Slows-Brain.pdf (668.2 KB)


Thanks, I’m planning to read this over the weekend. I have some ordered.

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I found a resent review article on a neuroprotective effect of MAO-B inhibitors, rasagilin and deprenyl.
There is not too much in the literature since 2012.

Neuroprotective Function of Rasagiline and Selegiline, Inhibitors of Type B Monoamine Oxidase, and Role of Monoamine Oxidases in Synucleinopathie

Makoto Naoi

Deprenyl is a very well tolerated medication with extremely rare side effects. It was very popular as a possible neuroprotecton for patients with early Parkinson’s disease in 2012 and later, but has been rarely used now. No obvious neuroprotection has been proven in multiple studies.

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A couple things to be aware of:

  1. The 1 mg daily dosage he mentions is for regular Deprenyl pills. It is NOT the oral disintegrating tablet, which is much more potent.

  2. Deprenyl (selegiline) liquid is under the brand name of DepPro. Not to be confused with Depo-Provera, the contraceptive. I haven’t found information on the pharmacokinetics of the liquid or if it can be absorbed in the mouth. So it seems important that it be mixed with a beverage and not dropped directly in the mouth unless there’s evidence it isn’t orally absorbed.


I took my first 1.25 mg dose this morning. The libido boost after 9-10 hours was a bit intense for me. Also as far as I know it shouldn’t work that quickly but nonetheless that was my experience. I’ve had 0-1 in that department on a scale of 1-10 for the last several years-no kidding-and actually made peace with it as no longer part of my life so this is a bit mind bending. I even had dreams of that nature during an afternoon nap (it’s a day off work). The only thing I can imagine is it lowered my prolactin but that seems pretty fast. @RapAdmin, please delete this if it’s inappropriate!


I don’t understand, what’s the difference between “regular Deprenyl pills” and “oral disintegrating tablets”? Is it the same pill taken differently (swallow with water vs dissolve on tongue) or are there sold as two different products? (I can only see 5mg selegiline hydrochloride tablets online, unclear whether these are tablets to swallow or dissolve)

The difference is that the orally disintegrating tablets rapidly dissolve in the mouth within seconds and are absorbed through the oral mucosa. It’s sold under the brand name Zelapar. It’s flavored (grapefruit) and sweetened.


I tried to source some but only found scam websites. Do you know of any legitimate sources?

Thanks. I assume there’s no generic version of Zelapar because it seems that everything I found on Indian marketplaces is normal tablets.

Trade names Eldepryl, Jumex, Zelapar, Emsam, others[1]


Has a generic version of Zelapar been approved?

No. There is currently no therapeutically equivalent version of Zelapar available in the United States.

But FDA approval in 2006, so generics available very, very soon - typically patents are issued a few years prior to FDA approval, so a generic may be available very soon, if its not already available in India (where generics typically come out first):

ZELAPAR (selegiline hydrochloride - tablet, orally disintegrating;oral)

  • Manufacturer: BAUSCH
    Approval date: June 14, 2006
    Strength(s): 1.25MG [RLD]

It seems there are lots of options at least for some versions, not sure on the disintegrating tablets - just search under the other names; selegeline, Eldepryl, etc with dissolving, and similar words?

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For example, conventional selegiline tablets had to be taken more than once daily. Not only did the conventional formulation have less than optimal efficacy, but it also presented a safety risk due to first-pass metabolite formation. The fast-dissolve formulation of selegiline, Zelapar, developed using Catalent’s Zydis orally disintegrating tablet technology, is absorbed buccally, thereby, avoiding first-pass metabolism and significantly reducing the potential for side effects. The ability to disintegrate in less than 3 seconds allows for increased bioavailability and a faster onset of action for Zelapar. The maximum blood levels of the drug (Tmax) were achieved in 15 minutes for Zelapar compared with 1 hour for the conventional selegiline pills. Moreover, dosing frequency could be reduced (i.e., 1.25 mg or 2.5 mg once daily compared with 5 mg twice daily for the conventional formulation).


Looks like the patent is expiring around now:

Source: Evergreen Drug Patent Database - UC College of the Law

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The first post under this topic has a paper by researcher Joseph Knoll who recommended 1 mg of “regular” Deprenyl per day for antiaging. The Life Extension Foundation “LEF” recommends daily dosages totalling 10 mg per week.

But the important point with regard to the above recommendations is that this is regular swallowed Deprenyl, NOT the orally dissolving tablet. For Parkinson’s, a common dosage is 5 mg regular Deprenyl twice daily. Or, 1.25 mg of the orally disintegrating pill twice daily. So that gives you an idea of the difference in potency and why they aren’t interchangeable.

There are some people who take higher dosages of Deprenyl for antiaging similar to a Parkinson’s patient. But LEF and Knoll both make arguments against this. Also, if someone does take a higher dosage, drug interactions have to be monitored.

Two rodent lifespan studies in mice and rats also found that polyscias fruticosa root had a synergistic effect with Deprenyl and helped to substantially increase the lifespan extension. I drink polyscias fruticosa tea daily. It’s the leaves and stems.


Yes, you can buy generics of Deprenyl/Selegiline (tablets to swallow) but not of Zelapar (orally disintegrating tablets). Pharmaceutical companies can often file a new patent if they change the route of administration and dosage of a drug.

As @Vlasko said, the ODT version is about 10 times more potent:

“To improve its bioavailability, new delivery forms of selegiline were also developed. Orally disintegrating tablets (ODT) are characterized by rapid drug release into saliva. A fraction of the active pharmaceutical ingredient absorbs through the buccal mucosa, avoiding thus the first pass metabolism and providing fast onset of action. According to comparative pharmacokinetic studies of conventional and ODT formulations, selegiline plasma exposure of 1.25 mg ODT was comparable to that of 10 mg conventional tablet. […] Comparative clinical trial of 1.25–2.5 mg selegiline ODT and 10 mg conventional tablets revealed similar efficacy and safety. […] By reviewing the available clinical data, we concluded that the clinical advantage of the clear pharmacokinetic improvement is not well justified. However, the patients’ preference, because of the convenience of ODT use, especially in patients with swallowing difficulties, should be acknowledged” (2019 review by Hungarian colleagues of late Knoll: Selegiline: a molecule with innovative potential | Journal of Neural Transmission )

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That’s interesting, thanks. There are so many details about Selegiline to use it correctly: route of administration (swallowed vs. disintegrating vs. skin patch), dosage (could be age dependent?), time of day, additional nutraceutical (e.g., polyscias fruticosa), etc.

We need an ITP for Selegiline for sure. But I think we also need a wiki where we could put all the information about Selegiline that is currently scattered over this forum (I think there are at least 3 threads discussing this drug for instance). And Wikipedia is quite conservative when it comes to medicine-related articles (see: Wikipedia:Manual of Style/Medicine-related articles - Wikipedia ). I’m among the most active contributors to Wikipedia and I don’t contribute in the longevity field because of this.

I googled “Longevity Wiki” and found one, I’ve just created a page about Selegiline, so feel free to contribute: Selegiline - Longevity Wiki


Yes - we have a couple of main Deprenyl threads, with a lot of information.

Here (86 posts in the thread): Deprenyl - Anti-Aging Drug Proven Effective in Dogs

Here (36 posts in the thread): Anyone taking Selegiline / Deprenyl For Longevity?

The longevity wiki guys are good and I applaud the effort, but they don’t seem to have critical mass yet.

For sure, you cannot have a critical mass for a wiki on such a niche topic as longevity. But we just need a few people centralizing interesting information currently scattered around this forum there from time to time. It would look like this: Selegiline - Longevity Wiki

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While writing the Wiki article I found two interesting articles:

The latter was just published by Hungarian researchers from Semmelweis University (the one of the late Knoll). They study BPAP, a deprenyl derivative and found no beneficial effects on cognitive capabilities or lifespan. They argue that their rats were under restricted food access and cognitively stimulated during the study so that they may have reached a ceiling in terms of lifespan and BPAP couldn’t go above that ceiling.

I wonder why they don’t study deprenyl anymore and instead study this derivative. They may have negative unpublished results about deprenyl. Typical publication bias: authors are more likely to submit positive results than negative ones. May be worth contacting them.

This seems to be the most recent animal study of selegiline, and it was done by Knoll two years before his death: Longevity study with low doses of selegiline/(−)-deprenyl and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP)

In this paper, he compared a saline solution to deprenyl (DEP) and a derivative devoid of MAO-B inhibitory effect: BPAP. Instead of 0.25 mg/kg three times a week as in previous studies, he tried lower doses of 0.001 mg/kg and 0.1 mg/kg.

Conclusions below: the lowest dose (0.001 mg/kg) had no significant effect (according to Knoll because 3 times per week may not be enough for low-dose deprenyl?), and the other one (0.1 mg/kg) increased the average lifespan by 12%. The life extension effect is mainly due to the increase in the life of the shortest-living rat: +28%!

I also contacted Dr. István at Semmelweis University to ask them to apply for an ITP of deprenyl (or BPAP if they think it’s better?).


Small Israeli study: IJMS | Free Full-Text | Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson’s Disease

tl;dr: Deprenyl + NAC improves Parkinson’s-like symptoms even more than Deprenyl alone.


blsm, I’ve decided to try Deprenyl at the 1.25 mg dose. Did you swallow the 1.25 mg dose or dissolve it under the tongue? Do you have any more thoughts on using it since your Apr 21 post? Thanks.