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Selegiline

Selegiline, better known by the trade-name Deprenyl, was discovered by a Hungarian scientist named Dr. Joseph Knoll in the 1960s.  Dr. Knoll initially developed Selegiline as a potential antidepressant, but the drug has since been approved for treatment for Parkinson's disease in many countries.[1]

 

A Canadian named Dr. Morton Shulman, who took the drug for Parkinson's disease in the late 1980s, reported that "deprenyl halted the course of his disease."[1]  After investigating the drug further, Dr. Shulman began to seek approval for the drug as a prophylactic life-extender for use in pets.[1,7]

 

Studies in rats and other animals have shown that a fairly lose dose of Selegiline can extend life greatly, as much as 30% or more.[5,7,8,9]  This is likely through at least two mechanisms: Selegiline inhibits production of MAO-B, a chemical responsible for breakdown of dopamine; as people and rats age, MAO-B breaks down dopamine more effectively (starting in the fourth decade of human life) and continues to increase progressively in effectiveness by about 13% each year.[3]  These effects are strikingly similar to the effects of Parkinson's disease, and studies have revealed that in elderly human brains the dopamine levels are often as low as a late-stage Parkinson's patient.[3]  Another possible mechanism responsible for the longevity effect demonstrated with Selegiline trials is that it "greatly increases" the antioxidant SOD or superoxide dismutase, one of the body's three major antioxidant systems.[1,4,5,8,9]  Inferences drawn from this should be framed against the strong possibility that increasing SOD without increasing glutathione peroxidase and catalase could be disruptive or harmful to the balance of bodily systems.[1]

 

Despite less-than-optimal results treating depression when taken orally, Selegiline has been proven to be "an effective and well-tolerated mono-amine oxidase inhibitor for the treatment of depression" when applied in a transdermal patch in doses as low as 6mg every 24 hours. [2]

 

Regarding application as an antidepressant, Culpepper and Kovalick conclude that:

The Selegiline transdermal system provides several advantages compared to orally administered MAOIs, including minimal interaction with dietary tyramine and prolonged exposure to the parent compound, while offering a favorable side effect profile. As a result, treatment at the lowest effective dose of 6 mg/24 hours can be administered without the need for dietary modifications.[2]

 

The history of Selegiline and its various uses provide insight into the drug approval process and even highlights medical biases in treatment options that are somewhat outside the scope of a research article, but nonetheless bear mentioning.  For further reading see resources [1,6].  Despite demonstrated effectiveness in Parkinson's treatment, Cotton observes that the drug is underutilized as a treatment, particularly in the critical beginning-stages of the disease in patients where early detection is achieved.[11]  Dr. Knoll  remains the greatest advocate of the drug for various use, which generates suspicion in the medical community where impartiality and objectivity are valued.[1,11]  Dr. Knoll's novel recommendation that Selegiline be prescribed as a prophylactic or preventative treatment for all middle-aged adults for Parkinson's and age-related decline has drawn mixed reactions, and is noteworthy for being the first medical recommendation of that type to come to light in the mainstream scientific community.[1,11]  From a policy perspective, since Selegiline is far from side-effect free (like most effective treatment options of any nature), the recommendation is controversial because any prophylactic drug administered to a largely healthy population must be weighed against the medical oath of "Primum non nocere" (First, do no harm).

 

Resources

[1]Emanuelson, Jerry.  "Deprenyl." (http://www.futurescience.com/deprenyl.html)

[2]Culpepper L, Kovalick LJ.  A review of the literature on the selegiline transdermal system: an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression.  Prim Care Companion J Clin Psychiatry. 2008;10(1):25-30.

[3]Knoll, J. "Deprenyl Medication: A Strategy To Modulate the Age-Related Decline of the Striatal Dopaminergic System" Journal of the American Geriatric Society. V.40., No.8, August, 1992, pp. 839-847.

[4]Kushleika, J. and others. "Selegiline and Lymphocyte Superoxide Dismutase Activities in Parkinson's Disease." V. 39, No.3, March, 1996. pp.378-381.

[5]Carrillo, M.C. and others. "Long Term Treatment with (-)Deprenyl Reduces the Optimal Dose as well as the Effective Dose Range for Increasing Antioxidant Enzyme Activities in Old Mouse Brain." Life Science. 1996: Vol.59, No.13. pp.1047-1057.

[6]Best, Ben.  "Can Deprenyl (Selegiline) Extend Human Lifespan?"http://www.benbest.com/lifeext/deprenyl.html

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

[8]M-C. Carrillo, et.al.  "(-)Deprenyl Increases Activities of

SuperOxide Dismutase and Catalase in certain Brain Regions in Old Male Mice."   Life Sciences, 54:975-981 (1994).

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

[10]Cotton, Paul. "Many Researchers, Few Clinicians, Using Drug That May Slow, Even Prevent, Parkinson's" Journal of the American Medical Association. Vol. 264, No. 9. Sept. 5, 1990. pp.1083-1084.

[11]Sonsalla, P.K. and Golbe L.I. "Deprenyl as Prophylaxis Against Parkinson's Disease?" Clinical Neuropharmacology. Vol. 11, No. 6., pp. 500-511.