Nice findings. Selegiline, you sexy beast, starting to feel more and more tempting.
What is the consensus on its amphetamine-metabolites, are they relevant when taking Selegiline in low-doses?
Posted 07 June 2023 - 10:33 AM
Nice findings. Selegiline, you sexy beast, starting to feel more and more tempting.
What is the consensus on its amphetamine-metabolites, are they relevant when taking Selegiline in low-doses?
Posted 07 June 2023 - 05:25 PM
https://en.wikipedia...methamphetamine
Apparently the enantiomeric effects are very dividing with amphetamine. The D-enantiomer has the predominant stimulant effects, whereas the L-enantiomer is much milder (and less rewarding).
I had to fact check a redditor, but (see wiki article) the L-enantiomer of methamphetamine is actually found in OTC products, such as nasal decongestants.
Since most selegiline is L-deprenyl, it wouldn't have much effect.
Even dosing D-deprenyl would only likely matter at large doses. I was using L-deprenyl in very small amounts. First week I used 5 mg (1.25 mg every other day). Then I took a week off before going through only 3.75 mg the next week.
The buccal or sublingual route of administration bypasses 95-98% of the liver metabolism. For a 500 mcg sublingual dose, scarcely enough amphetamine metabolites would be generated to affect a fruit fly. But you can see in the sci-hub study on the previous page, selegiline has a short half life compared to the amphetamine metabolites, so with the oral route they do build up to an extent and have a larger "area under curve" than selegiline itself.
My own belief is that the amphetamine metabolites have no measurable impact (good or bad) on micro-dose treatment, and that at the given level of exposure no negatives effects are known.
Posted 07 June 2023 - 10:04 PM
I wonder if this can also be avoided by lower doses of an irreversible inhibitor? Curiously, I am deficient in the DAO enzyme since early adulthood (but this is peripheral, I'm not sure about the CNS).
Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease
https://www.science..../sciadv.aav0316
Monoamine oxidase–B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer’s disease (AD) because of its association with aberrant γ-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.
Posted 13 February 2024 - 06:02 AM
I found a couple of curious studies from 2023. However, the concentrations used in the studies are far below the levels used for life extension or even for antidepressant purposes; it's not clear that the differentiation of stem cells into neurons plays a significant role in the clinical effect seen in humans, but it's interesting to contemplate and consider — among the growing body of positive research on this compound — the possibility that these mechanisms play a role.
Synergistic Effect of Lovastatin and Selegiline on the Differentiation of Bone Marrow Stromal Cells Into Neuron-Like Cells | Jentashapir Journal of Cellular and Molecular Biology | Full Text
Selegiline induced differentiation of rat bone marrow mesenchymal stem cells to dopaminergic neurons in vitro
And here are a few more studies — once again, all from 2023 or later.
Effect of selegiline as a monomine oxidase B inhibitor on the expression of neurotrophin mRNA levels in a contusion rat model of spinal cord injury: Neurological Research: Vol 45, No 3
"The results showed that administration of selegiline improves locomotor function and increases mRNA levels of BDNF, GDNF, NT-3, and NT-4."Neuroprotective Effects of Selegiline Agent Methamphetamine-Prompted Mood-Related Behavior Disorder : International Journal of Preventive MedicineSelegiline ameliorated dyslipidemia and hepatic steatosis in high-fat diet mice - ScienceDirectPharmaceutics | Free Full-Text | Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese MiceMAO – B Inhibitor “Selegiline” Attenuates Oxidative Stress and Arthritic Parameters in an Invitro Repurposed Studies | Journal of Biomedical Engineering
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