Selegiline article , Neuroprotective

This is an interesting read about Selegiline.

It is Neuroprotective according to the link below.

lifeextension.com/magazine/...

[Hidden]

This is a screen shot from the article.Study in Finland, deceased PWP brains examined. Selegiline looked to have Neuroprotective effects.

Selegiline

[Bolt_Upright]

That article is from 1996. Here is something from 2012: Selegiline: a reappraisal of its role in Parkinson disease pubmed.ncbi.nlm.nih.gov/225...

"Abstract

Selegiline at the doses used in Parkinson disease is a selective irreversible monoamine oxidase type B inhibitor, which potentiates dopaminergic function in the brain, and is used as monotherapy in early Parkinson disease or in combination with levodopa in more advanced disease. A renewed interest in monoamine oxidase type B inhibitors in the treatment of Parkinson disease has emerged after recent clinical trials of agents in this class. The use of selegiline monotherapy in early Parkinson disease is supported by the results of a large well-controlled trial in 800 patients (DATATOP) and several other studies, which demonstrated a symptomatic benefit, a reduction in disability, and a delay in the need to start levodopa therapy. Administered with levodopa in studies of up to 5 years' duration in patients with more advanced disease, selegiline improved disease-related disability, reduced the end-of-dose motor fluctuations, and also led to a reduction of the dose and dose frequency of levodopa required.Selegiline was the first drug to be investigated as a possible neuroprotective agent in patients with Parkinson disease, based on preclinical studies indicating protection of dopaminergic neurons from damage. The results of the extensive body of clinical trials, including delayed and lower levodopa requirements, may indeed suggest that selegiline, in addition to conferring symptomatic benefit, may have other effects on disease progression. Selegiline is well tolerated, and initial fears of increased mortality with the drug have not been borne out by subsequent robust meta-analyses."

[Hidden in reply to Bolt_Upright]

Thank you for the abstract. What I linked to is if interest bc although it is from 96, it is the basis upon which the current opinion of Selegiline is founded and details one of the largest in human studies for PD. Furthermore, it states that a dose much lower than what is prescribed for PD has neuro benefits in the non pd brain and I therefore wonder if a low dose would be good for very early or prodromal PD (like us)

[Bolt_Upright in reply to Hidden]

Ah, low dose selegiline. Interesting.

A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition 2003 pubmed.ncbi.nlm.nih.gov/146...

"Abstract

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001). Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25 mg (90%) or Zydis Selegiline 10 mg (86%) over conventional selegiline tablets 10 mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25 mg liked the taste compared with 45% taking Zydis Selegiline 5 mg (in the previous study). Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400 mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25 mg. In contrast, after 14 days treatment with conventional selegiline tablets 10 mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400 mg to 200 mg. In summary, Zydis Selegiline at doses of 1.25 mg and 10 mg was therapeutically equivalent to conventional selegiline tablets 10 mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25 mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine."

[park_bear]

That was an informative review of the studies of effect of deprenyl/selegiline. They were rightfully skeptical of the one study out of about a dozen that attributed increased death rate to deprenyl -the A J Lees study which can be found here:

ncbi.nlm.nih.gov/labs/pmc/a...

This study recruited patients with early Parkinson's disease who were not receiving dopaminergic treatment. A look at Figure 1 from the study, reproduced below, shows that the increased death rate occurred mainly between 2 1/2 to 3 1/2 years from their entry to the study. There is something wrong with this data because patients do not die naturally of Parkinson's so quickly. If deprenyl/selegiline were actually causing such early deaths someone would have noticed in the 25+ years since the study was done. If this were a natural effect one would expect steadily increasing divergence between the death rates as time progressed. Although there were a few divergent points at the six-year mark generally this was not the case. Also, the numbers listed for surviving patients below the chart match neither the chart nor the numbers in table 1.

Finally, as stated in the Life Extension article, the study reports: " During the trial the dose of levodopa required to produce optimum motor control steadily increased in arm 1 (median daily dose 375 mg at 1 year and 625 mg at 4 years), but median dose in arm 2 did not change (375 mg)." This extremely favorable result for deprenyl/selegiline is at odds with the increased death rate.

This result from a study of the brains of Parkinson's patients who had passed on supersedes all contrary evidence: "The present results show that the number of medial nigral neurons is greater and the number of Lewy bodies per neuron is smaller in those Parkinson's disease patients who had been treated with selegiline in combination with levodopa as compared with patients who had received levodopa alone. These findings indicate that the degeneration of the substantia nigra is less severe in patients who had had selegiline treatment."

No need to restrict oneself to take a low subtherapeutic dose of deprenyl/selegiline.

Access this attributed to selegiline from A J Lees study

[Hidden in reply to park_bear]

So, given what we know of Selegiline vs Azilect why are we prescribed Azilect now instead of Selegiline? I suspect that Selegiline is only generic so there is no push behind it for profit?

BTW, I’m on Azilect and I can’t tell if it’s doing anything.

[park_bear in reply to Hidden]

Azilect is also available in a generic as rasagiline.

At one time Azilect was thought to provide a reduction in disease progression but that has come under dispute. The Life Extension article is the first time I have made aware of the various benefits of selegiline. I do take it and perhaps that has something to do with my non-progression. Regarding day-to-day symptom relief both selegiline and Azilect provide only slight benefit in my experience.

[Hidden in reply to park_bear]

I would like to stop Azilect to see how I am without it to help me determine what has enabled my improvements. But I’m wary of stopping. Do I need a neuros support you think? Then I’m hoping to get Selegiline

[park_bear in reply to Hidden]

Since selegiline is a prescription med you are going to have to talk to your neurologist about it sooner or later anyway so you might as well discuss it now.

As far as I know there are no issues with stopping but I could be missing something.

[Bolt_Upright in reply to Hidden]

I think you might be right about the reasons not to prescribe selegiline. There is a TON of current information in this article: Selegiline: a molecule with innovative potential link.springer.com/article/1... just scroll down to this section "Clinical studies on selegiline in PD". There is SO MUCH in here.

For instance, it links to this study from 2010: Early Addition of Selegiline to L-Dopa Treatment is Beneficial for Patients With Parkinson Disease journals.lww.com/clinicalne...

"Conclusions:

The clinical outcome as evaluated by the selected UPDRS motor scores was better for L-Dopa-treated patients who received selegiline within 5 years from the onset compared with those who received selegiline approximately 10 years from the onset."

[Hidden in reply to Bolt_Upright]

You’ve lost me as to why that is reason not to?

[Bolt_Upright in reply to Hidden]

I was supporting your comment "I suspect that Selegiline is only generic so there is no push behind it for profit?". It does seem that they come out with new inferior drugs once patents expire.

I have a HS degree

[Hidden in reply to Bolt_Upright]

Got it! Bolt, I bet you found HS school boring? Just curious. I did. I was in the wrong place. It wasn’t stimulating so I rather checked out. Needing to have a college degree thiugh I got a useless but fun liberal arts and art degree. Looks good on paper, depleted savings and does nothing! ☺️

[Mimer in reply to Hidden]

One factor in the selection between Selegiline and Azilect could also be ones preferences to Meth and Amphetamine. During the break down of Selegiline in the brain low doses of those are created as bi product. I am on Selegiline since a two or three years' myself. I don't know the reason for why my neuro described that and not anything else. For around a year as monotherapy and later together with Levdopa.

[Likii]

The interesting article in the OP has been "Scientifically reviewed by: Dr. Gary Gonzalez, MD, in August 2023."

I don't know to what extent it has been altered.