EmSam (selegiline) may protect the brain, and can help those with depression feel “delightful” (HARVARD PSYCHIATRIST)

“Deprenyl (selegiline) protects the brain’s ‘engine of life’ – the vital dopaminergic system.”

“Remission From Depression With Delight”

Selegiline (l-deprenyl, Eldepryl, EmSam) is a drug used for the treatment of early-stage Parkinson’s Disease, depression, and senile dementia.  A new transdermal topical skin patch (EmSam) is FDA approved for treatment of major depression.


  1. EmSam  is a  new formulation of an old drug.  It is a patch that sticks to the skin.  The TOPICAL PATCH allows the drug  to slowly move through the skin, into the circulation. This negated the side effects of the old ORAL DOSING.
  2. EmSam is FDA approved for major depression (it is also used “off label” for ADHD, Parkinson’s, brain protection, and memory).
  3. Selegiline has been used in brain diseases: Alzheimer’s, Parkinson’s Disease, dementia, depression, and ADHD.
  4. EmSam is an anti-oxidant.
  5. Deprenyl (also known as selegiline, the active drug in EmSam) has been shown in some research studies to extend lifespan.  These studies have been called into question.
  6. MOA inhibitors TAKEN ORALLY (not TOPICALLY) have potentially serious side effects – tyramine in cheese can cause very high blood pressure.  EmSam (the skin patch) is absorbed through the skin and bypasses the GI tract, thus all but negating all the side effects of the oral forms.


  • Parkinson’s Disease
  • Brain protection
  • Depression
  • Early dementia – memory enhancement
  • ADHD
  • Possibly as a help to drug and alcohol withdrawal

The uses of selegiline are: Parkinson’s Disease, brain protection, depression, early dementia (memory improvement), and ADHD


For the newly diagnosed Parkinson’s patients, selegiline appears to slow the progression of the disease.  It delays the time point when the L-DOPA (levodopa) treatment becomes necessary from 10-12 to 18 months. The idea behind adding selegiline to levodopa is to decrease the dose of levodopa and thus reduce the motor complications of levodopa therapy. Comparisons of patients on levodopa + placebo vs levodopa + selegiline showed that selegiline allowed reduction of the levodopa dose by about 40%. Selegiline + levodopa also extended the time until the levodopa dose had to be increased from 2.6 to 4.9 years. As a result there were fewer motor complications in selegiline groups.

In one trial, selegiline + levodopa completely halted the progress of Parkinson’s disease over 14 months, while in the placebo + levodopa group the deterioration of the patients’ condition continued. However, the interpretation of this trial as proving neuroprotective action of selegiline has been questioned.

As of February 28, 2006, selegiline has also been approved by the FDA to treat major depression using a transdermal patch (EmSam Patch). Selegiline is also used (at extremely high dosages relative to humans) in veterinary medicine to treat the symptoms of Cushing’s Disease and cognitive dysfunction in dogs.  As of June 26, 2006, a selegiline transdermal patch is being tested for its effectiveness in treating ADHD.

Several clinical studies are currently underway to evaluate selegiline’s effectiveness in helping people stop smoking tobacco and marijuana.   J Neural Trans Supply 1998;52:99-107.


Desmethylselegiline may have neuroprotective antiapoptotic properties. A large multicenter study suggests a decrease in the disease progression of parkinsonism but may have reflected other symptomatic response. Desmethylselegiline is metabolized by CYP2C19.

L-amphetamine and L-methamphetamine

Selegiline is partly metabolized to l-methamphetamine.  This stereoisomer is not considered psychoactive and has little abuse potential. The stimulatory effect on locomotor activity and dopamine synthesis may be contributed to by the action of l-methamphetamine. If anyone is prescribed and takes selegiline, they can and will test positive for amphetamine / methamphetamine on most drug tests.


Study #1:  Neuroprotection

Neuroprotection by (-)-deprenyl  and related compounds

by Maruyama W, Naoi M , Department of Basic Gerontology,  National Institute for Longevity Sciences, Obu, Japan.  maruyama@nils.go.jp
Mech Ageing Dev 1999 Nov; 111(2-3):189-200


There is an increasing number of data by in vitro and in vivo experiments, indicating that (-)-deprenyl is neuroprotective to dopamine neurons, even though detailed mechanism remains to be clarified. In this paper neuroprotection by (-)-deprenyl and structurally related compounds was examined in concern with the suppression of apoptosis induced by a reactive oxygen species, peroxynitrite generated from SIN-1. The apoptotic DNA damage was quantitatively determined using dopaminergic SH-SYSY cells and by a single cell gel electrophoresis (comet) assay. DNA damage induced by peroxynitrite was proved to be apoptotic by prevention of the damage by cycloheximide or actinomycin-D. (-)-Deprenyl and other propargylamines protected the cells from apoptosis in a dose-dependent way. (-)-Deprenyl protected the cells even after it was washed out, suggesting that it may initiate the intracellular process to repress the apoptotic death program. The study on the structure-activity relationship of (-)-deprenyl analogues revealed that a N-propargyl residue with adequate size of hydrophobic structure is essentially required for the anti-apoptotic activity. These results suggest that (-)-deprenyl and related compounds may protect neurons from apoptosis and be applicable to delay the deterioration of neurons during advancing ageing and in neurodegenerative disorders.

Study 2: Neuroprotection, Preservation of Brain Cells

J Neural Transm Suppl. 1998;52:99-107.

Neuroprotection by selegiline and other MAO inhibitors. Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models
by Kitani K, Kanai S, Ivy GO, Carrillo MC, National Institute for Longevity Sciences,  Aichi, Japan.  Ann N Y Acad Sci 1998 Nov 20; 854:291-306


Among many pharmaceuticals that have been tested for their effects on longevities of different animal rodents, deprenyl is unique in that its effects on longevity has been tested in at least four different animal species by independent research groups and that the effect has been postulated to be due to its effect of raising such antioxidant enzyme activities as superoxide dismutase (SOD) and catalase (CAT) in selective brain regions. Thus far, in all four species of animals examined (rats, mice, hamsters, and dogs), a positive effect was demonstrated, although the extent of its effect is quite variable. Our group has examined the effect on longevities in rats and mice and on antioxidant enzymes in rats, mice, and dogs. Although in rats of both sexes, we have obtained positive effects on longevity, two studies with different doses in mice did not reveal a significantly positive effect. We have observed, however, significantly positive effects on SOD (in Cu, Zn-, and Mn-) as well as CAT (but not glutathione peroxidase) activities in the brain dopaminergic system such as in the S. nigra and striatum (but not in hippocampus) in all rats, mice, and dogs, although the effects were quite variable, depending on the doses used. In mice, however, a long-term administration (3x/w, 3 months) caused a remarkable decrease in the magnitude of activity as well as a narrowing of the effective dose range, which may explain a relatively weak effect of the drug on mouse longevity. Further, a recent study on aging beagle dogs by Ruehl et al. showed a remarkable effect on longevity, which agrees with our SOD study in dogs. Although deprenyl has been claimed to have several other effects, such as a radical scavenging effect and a neuroprotective effect, past reports on its effects on longevities and antioxidant defenses are compatible with the notion that the drug prolongs the life span of animals by reducing the oxidative damage to the brain dopaminergic system during aging. Further, our studies on F-344 rats as well as a dog study by Ruehl et al. suggest that the drug may at least partially prolong the life span of animals by enhancing immune system function and preventing tumor development in animals.

From the Life Extension Foundation:

Q: I understand that deprenyl is an irreversible MAO-B inhibitor. If I do not have Parkinson’s disease, could there be any danger to taking a drug that inhibits this enzyme?

A: Deprenyl is a selective irreversible inhibitor of the MAO-B enzyme, the type of MAO that damages brain cells during “normal” aging. MAO-B degrades dopamine and the depletion of dopamine is the primary factor in the genesis of Parkinson’s disease. Levels of MAO-B increase with advancing age in humans. The theory in taking deprenyl is to conserve dopamine in the brain [Fed Proc, 34:103-107, 1975]. It is also speculated that deprenyl might protect neurons in the brain by mechanisms other than inhibiting MAO-B. Scientists at the University of Toronto found that deprenyl given in doses too small to inhibit MAO-B, preserved neurons from functional damage in tissue culture [J. Neuroscience Res, 30:666-672, 1991, Neuroscience Res, 31:394-400, 1992, Neurochemistry in Clinical Applications, eds. Tang L and Yang S, p. 15-16, Plenum Press, NY 1995]. According to the Physician’s Desk Reference (PDR) 2002, the recommended dosage of deprenyl to effectively inhibit MAO-B, is 10 mgs per day. If you are taking deprenyl for anti-aging purposes, the Foundation recommends 5 mgs per week, which is only one-fourteenth the dosage for Parkinson’s disease. This dosage will not completely inhibit MAO-B, but is for anti-aging purposes. Animal and cell culture studies suggest that deprenyl may have neuroprotective and anti-aging effects.  Source: Life Extension Foundation

The following Article is from the Life Extension Foundation. www.lef.org

Youthful Brain, Youthful Body

Deprenyl has been shown not only to protect brain cells, but to extend life span as well. The synergistic effects are fascinating.
In 1988, Joseph Knoll published a paper reporting that with deprenyl-a substance known for its brain-protecting properties-he had more than doubled the remaining life expectancy of 24-month-old rats. A few years later, a Canadian group reported that the same dosage of deprenyl (the equivalent of 10 mg a day for a 170-pound person) also had extended the remaining life expectancy of laboratory animals.

How does deprenyl extend life span? More pointedly, why would a substance that prevents dopamine breakdown and protects neurons result in extended youth?

True, deprenyl has been shown to help Alzheimer’s patients live longer, and that can be attributed to its benefits to the brains of these patients. But it also extends the life spans of the healthy. How? It is only possible to guess, but as the ultimate regulator of hormones and the immune system, the brain can exert its effect on every cell in the body. A youthful brain may be the key to a youthful body.

Currently, only the L-form of this drug is in widespread clinical use, primarily for its ability to inhibit the B form of monoamine oxidase (MAO), an enzyme that functions in the brain to break down neurotransmitters. The A form, MAO-A, is found in most neurons and is most effective for breaking down the neurotransmitters serotonin, adrenaline and noradrenaline. MAO-B, by contrast, is found in non-neuron brain cells (glia cells called astrocytes) and is more effective in breaking down the neurotransmitter dopamine. Drugs that inhibit MAO-A are used as anti-depressants, whereas drugs that inhibit MAO-B are more effective as treatments for Parkinson’s disease.

It is quite an unexpected result that a MAO-B inhibitor could double the remaining life expectancy of normal animals. But recent studies continue to affirm the ability of deprenyl to extend remaining life span (although not to the extent of doubling) of both laboratory animals and Alzheimer’s disease patients.

When middle-aged female Syrian hamsters were given deprenyl dosages equivalent to 4 mg a day for a 170-pound person, the hamsters experienced a 16-percent increase in maximum life span (no effect was seen for males). Another experiment was conducted on elderly beagle dogs. When the dogs were given the equivalent of 77 mg a day for a 170-pound person, 80 percent survived to the end of the experiment, whereas only 39 percent of the placebo dogs survived. Studies of deprenyl on Syrian hamsters and Fischer 344 rats also have demonstrated improved spatial learning and long-term memory.

Further, one recent study of Alzheimer’s disease patients showed a 15-percent improvement in behavioral symptoms with 10 mg a day of deprenyl. Another study of Alzheimer’s patients receiving the same dose showed an increase in median survival of 215 days, compared with placebo.

The breakdown products of dopamine resulting from MAO-B degradation are hydrogen peroxide, ammonia and an aldehyde. Aldehydes are highly reactive compounds that can modify proteins. Ammonia is also toxic, particularly to glia (non-neuron brain cells). Hydrogen peroxide in the presence of ferrous iron ions can lead to hydroxyl radicals, the most toxic of all free radicals. Hydrogen peroxide can easily pass into the cell nucleus where it can encounter iron ions and produce hydroxyl radicals that damage and mutate DNA.

Besides causing MAO-B inhibition, deprenyl can increase the formation of the natural antioxidant enzymes superoxide dismutase (SOD) and catalase in the substantia nigra, striatum and cerebral cortex regions of the brain. Joseph Knoll has contended that it is this effect of deprenyl, rather than MAO-B inhibition, that results in life span extension.

Most deprenyl life span studies have been conducted on rats whose brains (unlike those of humans) use MAO-A, rather than MAO-B, to metabolize dopamine. Thus, inhibition of MAO-B metabolism of dopamine seems unlikely to be the mechanism by which deprenyl extends a rat’s life span. The dose of deprenyl required to cause the production of antioxidant enzymes is highly dependent upon the strain, age, sex and species of animal. The equivalent of 75 mg a day for a 170-pound person produced optimal superoxide dismutase in old C57BL male mice and female beagles.

Female Fischer 344 rats achieve maximum production at the equivalent of 15 mg a day for a 170-pound person. SOD and catalase activity is less for larger or smaller doses, meaning 15 mg a day is optimal. However, the optimal dose for male Fischer 344 rats is 10 times greater-the equivalent of 150 mg a day for a 170-pound person. Old female Fischer 344 rats, on the other hand, do best with the equivalent of about 75 mg a day. Dosages of the equivalent of 150 mg a day significantly decrease the activity of glutathione peroxidase in both old and young female Fischer 344 rats. Without glutathione peroxidase (or enough catalase) to eliminate hydrogen peroxide, SOD conversion of superoxide to hydrogen peroxide can lead to the formation of the deadly hydroxyl radical. The fact that both too much or too little deprenyl can reduce its antioxidant effect-and the fact that optimum dose varies so greatly with strain, age, sex and species-makes the prediction of optimal dosages for human beings on the basis of animal studies very difficult.

Whether or not deprenyl is a wonder drug, the multiplicity of its effects are certainly a cause for wonder.

In a 1990 Canadian life span study, it was noted that the control animals had significantly higher blood urea nitrogen (BUN), indicative of deprenyl’s protection of the kidney. Deprenyl protects neurons from hypoxia/ischemia damage.

The fact that both too much or too little deprenyl can reduce its antioxidant effect makes the prediction of optimal dosages for human beings very difficult.

Deprenyl increases cell levels of the natural antioxidant enzyme superoxide dismutase by direct alteration of gene/protein transcription/synthesis. By the same kind of direct action on DNA, deprenyl also increases nerve growth factors, proteins halting “cell suicide” (apoptosis) and other proteins involved in protecting neurons-40 or more such genes in all.

Life extensionists have understandably had a difficult time trying to determine what dose would be optimal for a human seeking the life-extension and neuroprotective benefits of deprenyl. Dosages in excess of 20 to 30 mg a day could create high blood pressure problems by MAO-A inhibition. Dosages in the 10 mg a day range would reduce the oxidation stress of the breakdown products of dopamine metabolized by MAO-B, but the resulting elevated dopamine levels might not be desirable.

Deprenyl binds to MAO-B irreversibly, and it takes two weeks for MAO-B levels to return to normal. A single 5-mg dose can cause 86 percent MAO-B inhibition within two to four hours. Inhibition remains at 90 percent for five days, and does not return to baseline for two weeks. Deprenyl induction of enzyme synthesis (including, presumably, antioxidant enzymes) can take place at levels below those required for MAO-B inhibition.

Therefore, a dose in the range of 1 mg a day might be optimal for a 40-year-old, 170-pound person. Twice-weekly dosing has been based on the fact that deprenyl binds MAO-B irreversibly, but more frequent dosing might be better for steady induction of enzyme synthesis.

Aside from body weight, age is a very important consideration. As a person gets older, neurons decrease in number, while glial cells (which synthesize MAO-B) increase. This means that MAO-B levels increase with age, which may be the reason that dopamine content of the striatum (caudate nucleus) typically decreases by 13 percent per decade after age 45. A person over 45 would want to counteract the excessive MAO-B in a dose proportional to his or her age. This could mean up to 5 mg daily for an elderly person with no symptoms of Parkinson’s or Alzheimer’s disease.

There may or may not be considerable individual variation in what is optimal. Decisions based on incomplete information are never very satisfying, but such decisions are, and will always be, a condition of life. The brain and body implications of deprenyl dosing will continue to fascinate.

Further Reading
“Longevity Study with (-)Deprenyl.” Joseph Knoll. Mech. of Aging and Development 46:237-262 (1988)

“Maintenance on L-Deprenyl Prolongs Life in Aged Male Rats.” Milgram, et al. Life Sciences 47:415-420 (1990)

“Chronic Treatment of (-)Deprenyl Prolongs the Life Span of Male Fischer 344 Rats.” K. Kitani, et al. Life Sciences 52:281-288 (1992)

“Sexually Low Performing Male Rats Die Earlier Than Their High Performing Peers and (-)Deprenyl Treatment Eliminates This Difference.” Joseph Knoll. Life Sciences 54:1047-1057 (1994)

“Chronic Treatment of Syrian Hamsters with Low-Dose Selegiline Increases Life Span in Females But Not Males.” S. Stoll, et al. Neurobiology of Aging 18:205-211 (1997)

“Treatment with L-Deprenyl Prolongs Life in Elderly Dogs.” W.W. Ruehl, et al. Life Sciences 61:1037-1044 (1997)

“Age-Related Memory Decline and Longevity under Treatment with Selegiline.” S. STOLL, et al. Life Sciences 25/26:2155-2163 (1994)

“Long-Term Treatment of Male F344 Rats with Deprenyl.” P.C. Bickford, et al. Neurobiology of Aging 18:309 -318 (1997)

“Selegiline in Treatment of Behavioral and Cognitive Symptoms of Alzheimer Disease.” S. Tolbert & M. Fuller The Annals of Pharmacotherapy 30:1122-1129 (1996)

“A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer’s Disease.” Mary Sano, et al. New England Journal of Medicine 336:1216-1222 (1997)

“2-Phenylethylamine: A Modulator of Catecholamine Transmission in the Mammalian Nervous System?” I.A. Paterson, et al. Journal of Neurochemistry 55:1827- 1837 (1990)

“(-)Deprenyl Increases Activities of SuperOxide Dismutase and Catalase in certain Brain Regions in Old Male Mice.” M-C. Carrillo, et al. Life Sciences 54:975-981 (1994)

“(-)Deprenyl Increases Activities of SuperOxide Dismutase (SOD) in Striatum of Dog Brain.” M-C. Carrillo, et al. Life Sciences 54:1483-1489 (1994)

“(-)Deprenyl Increases Activities of SuperOxide Dismutase and Catalase in Striatum but not Hippocampus.” M.C. Carrillo, et al. Experimental Neurology 116:286-294 (1992)

“Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampus.” H. Lahtinen, et al. Brain Research 757:260-267 (1997)

“(-)-Deprenyl Reduces PC12 Cell Apoptosis by Inducing New Protein Synthesis.” W.G. Tatton, et al. Journal of Neurochemistry 63:1572-1575 (1994)

“Effect of Deprenyl on the Progression of Disability in Early Parkinson’s Disease.” The Parkinson Study Group. New England Journal of Medicine 321:1364-1371 (1989)

“Effect of Tocopherol and Deprenyl on the Progression of Disability in Early Parkinson’s Disease.” The Parkinson Study Group. New England Journal of Medicine 328: 176-183 (1993)

“Impact of Deprenyl and Tocopherol Treatment on Parkinson’s Disease in DATATOP Subjects Not Requiring Levodopa.” The Parkinson Study Group. Annals of Neurology 39:29-36 (1996)

“Impact of Deprenyl and Tocopherol Treatment on Parkinson’s Disease in DATATOP Subjects Requiring Levodopa.” The Parkinson Study Group. Annals of Neurology 39:37-45 (1996)

“Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease.” A.J. Lees, et al. British Medical Journal 311:1602-1607 (1995)