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Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied and used off-label use for a variety of other indications, but has not been formally approved for any other use. The medication, in the form licensed for depression, has modest effectiveness for this condition that is similar to that of other . Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.
of selegiline occurring more often than with placebo include insomnia, dry mouth, dizziness, anxiety, abnormal abnormal dream, and application site reactions (with the patch form), among others. At high doses, selegiline has the potential for dangerous drug interaction, such as tyramine-related hypertensive crisis (the so-called "cheese reaction") and risk of serotonin syndrome. However, doses within the approved clinical range appear to have little to no risk of these interactions. In addition, the ODT and transdermal patch forms of selegiline have reduced risks of such interactions compared to the conventional oral form. Selegiline has no known abuse potential or drug dependence and is not a controlled substance except in Japan. (1996). 9783211828915 ISBN 9783211828915
Selegiline acts as a monoamine oxidase inhibitor (MAOI) and thereby increases levels of monoamine neurotransmitters in the brain. At typical clinical doses used for Parkinson's disease, selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B), increasing brain levels of dopamine. At higher doses, it loses its specificity for MAO-B and also inhibits monoamine oxidase A (MAO-A), which increases serotonin and norepinephrine levels in the brain as well. In addition to its MAOI activity, selegiline is a catecholaminergic activity enhancer (CAE) and enhances the action potential-mediated release of norepinephrine and dopamine in the brain. This action may be mediated by TAAR1 agonist. After administration, selegiline partially drug metabolism into levomethamphetamine and levoamphetamine, which act as norepinephrine releasing agents (NRAs) and may contribute to its therapeutic and adverse effects as well. The levels of these are much lower with the ODT and transdermal patch forms of selegiline. Chemically, selegiline is a substituted phenethylamine and amphetamine, a derivative of methamphetamine, and the enantiopure drug levorotatory enantiomer of deprenyl (the racemic mixture of selegiline and D-deprenyl). (1993). 9783034863490, Birkhäuser Basel. ISBN 9783034863490
Deprenyl was discovered and studied as an antidepressant in the early 1960s by Zoltan Ecseri, József Knoll, and other colleagues at Chinoin in Hungary. Subsequently, selegiline was purified from deprenyl and was studied and developed itself. Selegiline was first introduced for medical use, to treat Parkinson's disease, in Hungary in 1977. It was subsequently approved in the United Kingdom in 1982 and in the United States in 1989. The ODT was approved for Parkinson's disease in the United States in 2006 and in the European Union in 2010, while the patch was introduced for depression in the United States in 2006. Selegiline was the first selective MAO-B inhibitor to be discovered and marketed. In addition to its medical use, there has been interest in selegiline as a potential anti-aging drug and nootropic. However, effects of this sort are controversial and uncertain. Generic drug versions of selegiline are available in the case of the conventional oral form, but not in the case of the ODT or transdermal patch forms.
A 2023 systematic review and meta-analysis evaluated the effectiveness and safety of selegiline in the treatment of psychiatric disorders including depression. It included both randomized and non-randomized published clinical studies. The meta-analysis found that selegiline was more effective than placebo in terms of reduction in depressive symptoms ( = −0.96, k = 10, n = 1,308), response rates for depression improvement ( = 1.61, k = 9, n = 1,238), and response rates for improvement of depression with atypical features ( = 2.23, k = 3, n = 136). Oral selegiline was significantly more effective than the selegiline patch in terms of depressive symptom improvement ( = −1.49, k = 6, n = 282 vs. = −0.27, k = 4, n = 1,026, respectively; p = 0.03). However, this was largely due to older and less methodology rigorous trials that were at high risk for bias. Oral selegiline studies also often employed much higher doses than usual, for instance 20 to 60mg/day. The quality of evidence of selegiline for depression was rated as very low overall, very low for oral selegiline, and low to moderate for transdermal selegiline. For comparison, meta-analyses of other antidepressants for depression have found a mean effect size of about 0.3 (a small effect), which is similar to that with transdermal selegiline.
In two pivotal regulatory clinical trials of 6 to 8weeks duration, the selegiline transdermal patch decreased scores on depression rating scales (specifically the 17- and 28-item ) by 9.0 to 10.9points, whereas placebo decreased scores by 6.5 to 8.6points, giving placebo-subtracted differences attributable to selegiline of 2.4 to 2.5points. A 2013 quantitative review of the transdermal selegiline patch for depression, which pooled the results of these two trials, found that the placebo-subtracted number needed to treat (NNT) was 11 in terms of depression response (>50% reduction in symptoms) and 9 in terms of remission of depression (score of ≤10 on the ). For comparison, other antidepressants, including fluoxetine, paroxetine, duloxetine, vilazodone, adjunct therapy aripiprazole, olanzapine/fluoxetine, and extended-release quetiapine, have NNTs ranging from 6 to 8 in terms of depression response and 7 to 14 in terms of depression remission. On the basis of these results, it was concluded that transdermal selegiline has similar effectiveness to other antidepressants. NNTs are measures of effect size and indicate how many individuals would need to be treated in order to encounter one additional outcome of interest. Lower NNTs are better, and NNTs corresponding to Cohen's d effect sizes have been defined as 2.3 for a large effect (d = 0.8), 3.6 for a medium effect (d = 0.5), and 8.9 for a small effect (d = 0.2). The effectiveness of transdermal selegiline for depression relative to and discontinuation was considered to be favorable.
While several large regulatory clinical trials of transdermal selegiline versus placebo for depression have been conducted, there is a lack of trials comparing selegiline to other antidepressants. Although multiple doses of transdermal selegiline were assessed, a dose–response relationship for depression was never established. Transdermal selegiline has shown similar clinical effectiveness in the treatment of atypical depression relative to typical depression and in the treatment of anxious depression relative to non-anxious depression.
Transdermal selegiline does not cause sexual dysfunction and may improve certain domains of sexual function, for instance sexual desire, maintaining interest during sex, and sexual satisfaction. These benefits were apparent in women but not in men. The lack of sexual dysfunction with transdermal selegiline is in contrast to many other antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), which are associated with high rates of sexual dysfunction.
Transdermal selegiline patches have been underutilized in the treatment of depression compared to other antidepressants. A variety of factors contributing to this underutilization have been identified. One major factor is the very high cost of transdermal selegiline, which is often not covered by insurance and frequently proves to be prohibitive. Conversely, other widely available antidepressants are much cheaper in comparison.
The transdermal patch form is also known as the "selegiline transdermal system" or "STS" and is applied once daily. They are 20, 30, or 40cm2 in size and contain a total of 20, 30, or 40mg selegiline per patch (so 20mg/20cm2, 30mg/30cm2, and 40mg/40cm2), respectively. The selegiline transdermal patch is a matrix-type adhesive patch with a three-layer structure. It is the only approved non-oral MAOI, having reduced dietary restrictions and in comparison to oral MAOIs, and is also the only approved non-oral first-line antidepressant. The selegiline patch can be useful for those who have difficulty tolerating oral medications.
Consumption of tyramine-rich foods can result in hypertensive crisis with selegiline, also known as the "cheese effect" or "cheese reaction" due to the high amounts of tyramine present in some cheeses. Examples of other foods that may have high amounts of tyramine and similar substances include yeast products, chicken liver, snails, pickled herring, red wines, some beers, canned figs, broad beans, chocolate, and cream products.
The preceding drug and food contraindications are dependent on selegiline dose and route, and hence are not necessarily absolute contraindications. While high oral doses of selegiline (≥20mg/day) can cause such interactions, oral doses within the approved clinical range (≤10mg/day) appear to have little to no risk of these interactions. In addition, the ODT and transdermal forms of selegiline have reduced risks of such interactions compared to the conventional oral form.
Selegiline is also contraindicated in children less than 12years of age and in people with pheochromocytoma, both due to heightened risk of hypertensive crisis. For all human uses and all forms, selegiline is pregnancy category C, meaning that studies in pregnancy animals have shown adverse effects on the fetus but there are no adequate studies in humans.
The main side effects of the patch form for depression include application-site reactions, insomnia, dry mouth, dizziness, nervousness, and abnormal dreams. The selegiline patch carries a boxed warning about a possible increased risk of suicide, especially for young people, as do all since 2007.
Side effects of selegiline that have been identified as occurring significantly more often than with placebo group in meta-analysis for psychiatric disorders have included xerostomia ( = 1.58), insomnia ( = 1.61, = 19), and application site reactions with the transdermal form ( = 1.81, = 7). No significant diarrhea, headache, dizziness, nausea, sexual dysfunction, or weight gain were apparent in these meta-analyses.
Selegiline, including in its oral, ODT, and patch forms, has been found to cause hypotension or orthostatic hypotension in some individuals. In a clinical trial, the rate of systolic orthostatic hypotension was 21% versus 9% with placebo and the rate of diastolic orthostatic hypotension was 12% versus 4% with placebo in people with Parkinson's disease taking the ODT form of selegiline. The risk of hypotension is greater at the start of treatment and in the elderly (3% vs. 0% with placebo). The rate of hypotension or orthostatic hypotension with the selegiline patch was 2.2% versus 0.5% with placebo in clinical trials of people with depression. Significant orthostatic blood pressure changes (≥10mmHg decrease) occurred in 9.8% versus 6.7% with placebo, but most of these cases were asymptomatic and heart rate was unchanged. The rates of other orthostatic hypotension-related side effects in this population were dizziness or vertigo 4.9% versus 3.1% with placebo and fainting 0.5% versus 0.0% with placebo. It is said that orthostatic hypotension is rarely seen with the selegiline transdermal patch compared to oral MAOIs. Caution is advised against rapidly rising after sitting or lying, especially after prolonged periods or at the start of treatment, as this can result in fainting. Falls are of particular concern in the elderly. MAOIs like selegiline may lower blood pressure by increasing dopamine levels and activating dopamine receptors, by increasing levels of the false neurotransmitter octopamine, and/or by other mechanisms. (2025). 9780123864673 ISBN 9780123864673
Meta-analyses published in the 1990s found that the addition of selegiline to levodopa increased mortality rate in people with Parkinson's disease. However, several subsequent meta-analyses with more trials and patients found no increase in mortality with selegiline added to levodopa. If selegiline does increase mortality, it has been theorized that this may be due to cardiovascular side effects, such as its amphetamine-related sympathomimetic effects and its MAO inhibition-related hypotension. Although selegiline does not seem to increase mortality, it appears to worsen cognition in people with Parkinson's disease over time. Conversely, rasagiline does not seem to do so and can enhance cognition.
Rarely, selegiline has been reported to induce or exacerbate impulse control disorders, problem gambling, hypersexuality, and in people with Parkinson's disease. However, MAO-B inhibitors like selegiline causing impulse control disorders is uncommon, controversial, and less frequent than with dopamine receptor agonists like pramipexole. Impulse control disorders with dopaminergic agents have been linked specifically to activation of dopamine D3 receptors in the globus pallidus. Selegiline has also been reported to activate or worsen rapid eye movement (REM) sleep behavior disorder (RBD) in some people with Parkinson's disease.
Selegiline has shown little or no abuse potential in humans or monkeys. Likewise, it has no drug dependence potential in rodents. This is in spite of its amphetamine active metabolites, levomethamphetamine and levoamphetamine, and is in contrast to agents like dextroamphetamine and dextromethamphetamine. However, selegiline can strongly potentiate the reinforcing effects of exogenous β-phenethylamine by inhibiting its MAO-B-mediated metabolism. Misuse of the combination drug of selegiline and β-phenethylamine has been reported.
All three forms of selegiline carry warnings about food restrictions to avoid hypertensive crisis that are associated with MAOIs. The patch form was created in part to overcome food restrictions; clinical trials showed that it was successful. Additionally, in post-marketing surveillance from April 2006 to October 2010, only 13self-reports of possible hypertension events or hypertension were made out of 29,141exposures to the drug, and none were accompanied by objective clinical data. The lowest dose of the patch method of delivery, 6mg/24hours, does not require any dietary restrictions. Higher doses of the patch and oral formulations, whether in combination with the older non-selective MAOIs or in combination with the reversible MAO-A inhibitor (RIMA) moclobemide, require a low-tyramine diet.
A study found that selegiline in transdermal patch form did not importantly modify the pharmacodynamic effects or pharmacokinetics of the sympathomimetic agents pseudoephedrine and phenylpropanolamine. Likewise, oral selegiline at an MAO-B-selective dosage did not appear to modify the pharmacodynamic effects or pharmacokinetics of intravenous methamphetamine in another study. Conversely, selegiline, also at MAO-B-selective doses, has been found to reduce the physiological and euphoric subjective effects of cocaine whilst not affecting its pharmacokinetics in some studies but not in others. Cautious safe combination of MAOIs like selegiline with psychostimulant like lisdexamfetamine has been reported. However, a hypertensive crisis with selegiline and ephedrine has also been reported. The selegiline drug labels warn about combination of selegiline with indirectly acting sympathomimetic agents, like amphetamines, ephedrine, pseudoephedrine, and phenylpropanolamine, due to the potential risk of hypertensive crisis, and recommend monitoring blood pressure with such combinations. The combination of selegiline with certain other medications, like phenylephrine and buspirone, is also warned against for similar reasons. In the case of phenylephrine, this drug is substantially metabolized by monoamine oxidase, including by both MAO-A and MAO-B. Selegiline can interact with exogenous dopamine, which is metabolized by MAO-A and MAO-B, and result in hypertensive crisis as well. (2025). 9780444506740, Elsevier. ISBN 9780444506740
Besides norepinephrine releasing agents, selective norepinephrine reuptake inhibitors (NRIs) may be safe in combination with MAOIs like selegiline. Potent NRIs, such as reboxetine, desipramine, protriptyline, and nortriptyline, can reduce or block the pressor effects of tyramine, including in those taking MAOIs. This is by inhibiting the norepinephrine transporter (NET) and preventing entry of tyramine into presynaptic noradrenergic where tyramine induces the release of norepinephrine. As a result, NRIs may reduce the risk of tyramine-related hypertensive crisis in people taking MAOIs. Norepinephrine–dopamine reuptake inhibitors (NDRIs), like methylphenidate and bupropion, are also considered to be safe in combination with MAOIs. However, initiation at low doses and slow upward dose titration is advisable in the case of both NRIs and NDRIs due to possible potentiation of their effects and side effects by MAOIs.
Selegiline may potentiate the effects of serotonergic psychedelics that are MAO-B substrates, such as 2C drugs like 2C-B, 2C-I, and 2C-E.
Birth control pills containing the synthetic estrogen ethinylestradiol and a progestin like gestodene or levonorgestrel have been found to increase peak levels and overall exposure to oral selegiline by 10- to 20-fold. High levels of selegiline can lead to loss of MAO-B selectivity and inhibition of MAO-A as well. This increases susceptibility to side effects and interactions of non-selective monoamine oxidase inhibitors (MAOIs), such as tyramine-induced hypertensive crisis and serotonin toxicity when combined with serotonin medications. However, this study had a small sample size of four individuals as well as other methodology limitations. The precise mechanism underlying the interaction is unknown, but is likely related to cytochrome P450 inhibition and consequent inhibition of selegiline first-pass metabolism by ethinylestradiol. In contrast to birth control pills containing ethinylestradiol, menopausal hormone therapy with estradiol and levonorgestrel did not modify peak levels of selegiline and only modestly increased overall exposure (+59%). Hence, menopausal hormone therapy does not pose the same risk of interaction as ethinylestradiol-containing birth control pills when taken together with selegiline.
Overall exposure to selegiline with oral selegiline has been found to be 23-fold lower in people taking known to strongly activate drug-metabolizing enzymes. The anticonvulsants included phenobarbital, phenytoin, carbamazepine, and amobarbital. In a previous study however, carbamazepine specifically did not reduce selegiline exposure. Phenobarbital and certain other anticonvulsants are known to strongly induce CYP2B6, one of the major enzymes believed to be involved in selegiline metabolism. As such, it was concluded that strong CYP2B6 induction was most likely responsible for the dramatically reduced exposure to selegiline observed in the study.
Selegiline is a small-molecule compound, with the molecular formula C13H17N and a low molecular weight of 187.281g/mol. It has high lipophilicity, with an experimental log P of 2.7 and predicted log P values of 2.9 to 3.1. Pharmaceutically, selegiline is used almost always as the hydrochloride salt, though the free base form has also been used. At room temperature, selegiline hydrochloride is a white to near white crystalline powder. Selegiline hydrochloride is freely solubility in water, chloroform, and methanol.
Rasagiline (( R)- N-propargyl-1-aminoindan) is an analogue of selegiline in which the amphetamine base structure has been replaced with a 1-aminoindan structure and the N-methyl group has been removed. Like selegiline, it is also a selective MAO-B inhibitor and used to treat Parkinson's disease. In contrast to selegiline however, rasagiline lacks the amphetamine metabolites and activity of selegiline. A further derivative of rasagiline, ladostigil ( N-propargyl-(3 R)-aminoindan-5-yl- N-propylcarbamate), a dual MAO-B inhibitor and acetylcholinesterase inhibitor, was developed for treatment of Alzheimer's disease and other conditions but was ultimately never introduced for medical use.
Deprenyl is a racemic mixture compound (a mixture of two called ). The racemic form has mild amphetamine-like psychostimulant effects that are diminished compared to those of amphetamine but are still present. The levorotatory enantiomer has further reduced stimulant effects, and further work, published in 1967, determined that the levorotatory enantiomer was a more potent MAOI than the dextrorotatory enantiomer. As a result, subsequent work was done with the single enantiomer L-deprenyl. (2025). 9780340761106, Arnold. ISBN 9780340761106 In 1968, it was discovered by J. P. Johnston that monoamine oxidase exists in multiple forms. In 1971, Knoll showed that selegiline highly selectively inhibits the B-isoform of monoamine oxidase (MAO-B) and proposed that it is unlikely to cause the infamous "cheese effect" (hypertensive crisis resulting from consuming foods containing tyramine) that occurs with non-selective MAOIs. The lack of potentiation of tyramine effect by deprenyl had previously been reported in 1966 and 1968 studies, but could not be mechanistically explained until after the existence of multiple forms of MAO was discovered. Selegiline was the first selective MAO-B inhibitor to be discovered and hence is described as prototypical of these agents.
Deprenyl and selegiline were initially studied as for treatment of depression. Deprenyl was first found to be effective for depression from 1965 to 1967, while selegiline was first found to be effective for depression in 1971 and this was further corroborated in 1980. A 1984 study that combined selegiline with phenylalanine reported remarkably high effectiveness in the treatment of depression similar to that with electroconvulsive therapy (ECT). However, selegiline in its original oral form was never further developed or approved for the treatment of depression.
A few years after the discovery that selegiline was a selective MAO-B inhibitor, two Parkinson's disease researchers based in Vienna, Peter Riederer and Walther Birkmayer, realized that selegiline could be useful in Parkinson's disease. One of their colleagues, Moussa B. H. Youdim, visited Knoll in Budapest and took selegiline from him to Vienna. In 1975, Birkmayer's group published the first paper on the effect of selegiline in Parkinson's disease.
Speculation, by József Knoll, that selegiline could be useful as an anti-aging and aphrodisiac, began in the 1980s. The New York Times reported that selegiline was being used non-medically as a nootropic by 1992.
Selegiline was first introduced for clinical use in Hungary in 1977. It was approved in the oral pill form under the brand name Jumex to treat Parkinson's disease. The drug was then introduced in the United Kingdom in 1982. In 1987, Somerset Pharmaceuticals in New Jersey, which had acquired the rights to develop selegiline in the United States, filed a New Drug Application (NDA) with the Food and Drug Administration (FDA) to market the drug for Parkinson's disease in this country. (2025). 9781611682694, University Press of New England. ISBN 9781611682694 While the NDA was under review, Somerset was acquired in a joint venture by two generic drug companies, Mylan and Bolan Pharmaceuticals. Selegiline was approved for Parkinson's disease by the FDA in 1989.
It had been known since the mid-1960s that high doses of deprenyl had psychostimulant effects. Selegiline was first shown to metabolism into levomethamphetamine and levoamphetamine in humans in 1978. The involvement of these metabolites in the effects and side effects of selegiline has remained controversial and unresolved in the decades afterwards. In any case, concerns about these metabolites have contributed to the development of newer MAO-B inhibitors like rasagiline and safinamide that lack such metabolites.
The catecholaminergic activity enhancer (CAE) effects of selegiline became well-characterized and distinctly named in 1994. These effects had been observed much earlier, dating back to the 1960s and 1970s, but were not properly distinguished from the other actions of selegiline, like MAO-B inhibition, until the 1990s. (2025). 9783540239697, Springer-Verlag. ISBN 9783540239697 More potent, selective, and/or expansive monoaminergic activity enhancers (MAEs), like phenylpropylaminopentane (PPAP) and benzofuranylpropylaminopentane (BPAP), were derived from selegiline and other compounds and were first described in 1988 and 1999, respectively. These drugs had been proposed for potential treatment of psychiatric disorders like depression as well as for Parkinson's disease and Alzheimer's disease, but were never developed or marketed.
In the 1990s, J. Alexander Bodkin at McLean Hospital, an affiliate of Harvard Medical School, began a collaboration with Somerset to develop delivery of selegiline via a transdermal patch in order to avoid the well known dietary restrictions of MAOIs. Somerset obtained FDA approval to market the patch for depression in 2006. Similarly, the orally disintegrating tablet (ODT) form of selegiline, marketed under the brand name Zelapar, was approved for Parkinson's disease in the United States in 2006 and in the European Union in 2010.
Binding to and agonism of the trace amine-associated receptors (TAARs) as the mechanism responsible for the MAE effects of selegiline and related MAEs like PPAP and BPAP was first suggested in the early 2000s following the discovery of the TAARs. Activation of the TAAR1 as the mechanism of the MAE effects was first clearly substantiated in 2022.
Major brand names of selegiline include Eldepryl, Jumex, and Movergan (oral tablet and/or capsule), Zelapar (orally disintegrating tablet or ODT), and Emsam (transdermal patch). Selegiline has been marketed under more than 70brand names worldwide. The brand name "Emsam" was derived from the names of two children, Emily and Samuel, of one of the executives at Somerset Pharmaceuticals, the developer of Emsam.
David Pearce, a British transhumanist philosopher, wrote his self-published book-length internet manifesto The Hedonistic Imperative six weeks after starting to take selegiline.
Sam Bankman-Fried, the founder and former CEO of the FTX cryptocurrency exchange, is known to have used selegiline for depression in the form of the Emsam patch for at least 5 to 10years. He is also known to have simultaneously taken Adderall for treatment of attention deficit hyperactivity disorder (ADHD) and to have possessed non-pharmaceutical adrafinil, a prodrug of modafinil.
"In humans, maintenance from sexual maturity on (–)-deprenyl (1mg daily) is, for the time being, the most promising prophylactic treatment to fight against the age related decay of behavioral performances, prolonging life, and preventing or delaying the onset of age-related neurodegenerative diseases such as Parkinson's and Alzheimer's".
The mechanism of selegiline's longevity-promoting effect has been researched by several groups, including Knoll and his associates at Semmelweis University, Budapest. The drug has been determined to be a catecholaminergic activity enhancer when present in minuscule concentrations far below those at which monoamine oxidase inhibitory activity can be observed, thereby potentiating the release of catecholamine neurotransmitters in response to stimuli. Knoll maintains that micro-doses of selegiline act as a synthetic analogue to a known or unknown trace amine in order to preserve the brain catecholaminergic system, which he perceives as integral to the organism's ability to function in an adaptive, goal-directed and motivated manner during advancing physical age:
"... enhancer regulation in the catecholaminergic brain stem neurons plays a key role in controlling the uphill period of life and the transition from adolescence to adulthood. The results of our longevity studies support the hypothesis that quality and duration of life rests upon the inborn efficiency of the catecholaminergic brain machinery, i.e. a high performing, long-living individual has a more active, more slowly deteriorating catecholaminergic system than its low performing, shorter living peer. Thus, a better brain engine allows for a better performance and a longer lifespan."
"Since the catecholaminergic and serotonergic neurons in the brain stem are of key importance in ensuring that the mammalian organism works as a purposeful, motivated, goal-directed entity, it is hard to overestimate the significance of finding safe and efficient means to slow the decay of these systems with passing time. The conclusion that the maintenance on (–)-deprenyl that keeps the catecholaminergic neurons on a higher activity level is a safe and efficient anti-aging therapy follows from the discovery of the enhancer regulation in the catecholaminergic neurons of the brain stem. From the finding that this regulation starts working on a high activity level after weaning and the enhanced activity subsists during the uphill period of life, until sexual hormones dampen the enhancer regulation in the catecholaminergic and serotonergic neurons in the brain stem, and this event signifies the transition from developmental longevity into postdevelopmental longevity, the downhill period of life."
Despite findings by Knoll that selegiline can prolong lifespan in rodents by 35% however, other studies have had conflicting findings and have even found increased mortality rate with selegiline in rodents. In humans with Parkinson's disease, selegiline has been associated with cardiovascular and psychiatric complications and has not been found to reduce mortality in long-term studies. As such, the claimed anti-aging and longevity benefits of selegiline have yet to be substantiated in humans and are controversial and uncertain.
Selegiline has also been reported to protect against methylenedioxymethamphetamine (MDMA)-induced serotonergic neurotoxicity in rodents. The serotonergic neurotoxicity of MDMA appears to be dependent on release of dopamine and its subsequent metabolism by MAO-B within serotonergic neurons into , which is blocked by MAO-B inhibition. Likewise, selegiline prevented the serotonergic neurotoxicity of a combination of methylenedioxyaminoindane (MDAI) and dextroamphetamine.
Conversely, selegiline failed to reduce the serotonergic neurotoxicity caused by fenfluramine and either did not affect or potentiated the serotonergic neurotoxicity caused by para-chloroamphetamine (PCA). In addition, findings are mixed and conflicting on whether selegiline prevents amphetamine- and methamphetamine-induced dopaminergic neurotoxicity in rodents. (1997). 9781461374688, Springer US. ISBN 9781461374688
Although MAO-B-selective doses of selegiline protect against MDMA-induced serotonergic neurotoxicity in rodents, combination of amphetamines like MDMA with MAOIs, including selegiline, can produce serious complications, including serotonin syndrome, hypertensive crisis, and death.
CCD is a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleep, reduced urinary incontinence, and increased activity level, with most showing improvements by one month of treatment. Though it is labeled for use in dogs only, selegiline has been used off-label use for geriatric cats with cognitive dysfunction.
PDH is a hormonal disorder and is analogous to pituitary gland-dependent Cushing's syndrome in humans. Selegiline's effectiveness in treating PDH has been disputed. Theoretically, it works by increasing dopamine levels, which downregulation the secretion of adrenocorticotropic hormone (ACTH) from the brain, eventually leading to reduced levels of cortisol. Some claim that selegiline is only effective at treating PDH caused by in the anterior pituitary (which comprise most canine cases). The greatest sign of improvement is lessening of PDH-related abdominal distention.
in dogs are uncommon, but they include vomiting, diarrhea, hearing loss, salivation, weight loss, and behavior such as hyperactivity, listlessness, disorientation, and stereotypy.
Selegiline has been limitedly studied in large animals like and its dosage in these animals has not been established. In preliminary research, a dose of selegiline of 30mg orally or intravenously in horses had no observable effects on behavior or locomotor activity.
The doses of selegiline used in animals are described as extremely high relative to those used in humans (which are ~0.1mg/kg body weight).
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