Selegiline

Mech Ageing Dev 2002 Apr 30;123(8):1087-100
Why (--)deprenyl prolongs survivals of experimental animals: increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects
Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC
National Institute for Longevity Sciences, 36-3, Gengo, Morioka-cho, Obu-shi, Aichi 474-8522, Japan. kitani@nils.go.jp

(--)Deprenyl, a monoamine oxidase B (MAO B) inhibitor is known to upregulate activities of anti-oxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions. The drug is also the sole chemical which has been repeatedly shown to increase life spans of several animal species including rats, mice, hamsters and dogs. Further, the drug was recently found to enhance anti-oxidant enzyme activities not only in brain dopaminergic regions but also in extra-brain tissues such as the heart, kidneys, adrenal glands and the spleen. We and others have also observed mobilization of many humoral factors (interferone (INF)-gamma, tumor necrosis factor (TNF)-alpha, interleukine (IL)-1beta,2,6, trophic factors, etc.) and enhancement of natural killer (NK) cell functions by (-)deprenyl administration. An apparent extension of life spans of experimental animals reported in the past may be better explained by these new observations that (-)deprenyl upregulate SOD and CAT activities not only in the brain but also in extra-brain vital organs and involve anti-tumorigenic as well as immunomodulatory effect as well. These combined drug effects may lead to the protection of the homeostatic regulations of the neuro-immuno-endocrine axis of an organism against aging.

Ann Neurol 2002 May;51(5):604-12
Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial
Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P, Olanow CW, Penney JB, Tanner C, Kieburtz K, Rudolph A; Parkinson Study Group
University of Rochester Medical Center, Rochester, NY 14620, USA

Deprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the long-term benefits of this treatment remain unclear. During 1987 to 1988, 800 patients with early Parkinson's disease were randomized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl, tocopherol, combined treatments, or a placebo and were then placed on active deprenyl (10mg/day). A second, independent randomization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment (D subjects) or changing to a matching placebo (P subjects) under double-blind conditions. The first development of wearing off, dyskinesias, or on-off motor fluctuations was the prespecified primary outcome measure. During the average 2-year follow-up, there were no differences between the treatment groups with respect to the primary outcome measure (hazard ratio, 0.87; 95% confidence interval, 0.63, 1.19; p = 0.38), withdrawal from the study, death, or adverse events. Although 34% of D subjects developed dyskinesias and only 19% of P subjects did (p = 0.006), only 16% of D subjects developed freezing of gait but 29% of P subjects did (p = 0.0003). Decline in motor performance was less in D subjects than P subjects. Levodopa-treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait.

Generic Name: deprenyl
Product Brand Name: Eldepryl ®, Selegeline ®, Jumex ®

1. Description: Eldepryl works by helping to conserve the amount of dopamine available by preventing the dopamine from being destroyed. While controversial, there is some evidence that this drug may slow the progression of Parkinson's disease, particularly early in the course of the disease. This drug is well-tolerated by most people, so many experts recommend using it despite the controversies.

2. Prescribed for: Eldepryl is used to treat Parkinson's disease. Parkinson's disease is associated with low levels of a chemical called dopamine (doe PA meen) in your brain. The exact way that eldepryl works is unknown. However, it is believed that eldepryl prevents the breakdown of dopamine in your brain. Eldepryl is usually added to a treatment regimen after levodopa / carbidopa therapy begins to deteriorate.

Eldepryl is also used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease. It is also used to treat the same muscular conditions when they are caused by drugs such as chlorpromazine (Thorazine), fluphenazine (Prolixin), perphenazine (Trilafon), and others.
Eldepryl may also be used for purposes other than those listed in this medication guide.

3. Drug Mechanism: Eldepryl provides selective protection against the age-related degeneration of the dopaminergic nervous system. It protects sensitive dopamine-containing neurons from the age-associated increases in glial cells (non-neuron brain cells) and the monoamine oxidase (type B) that they contain. Eldepryl is the first selective inhibitor of MAO-B ever discovered, it is the only one used in clinical practice, and it remains the scientific reference standard for B-type inhibition after more than 40 years.

Eldepryl also competitively inhibits the uptake of dopamine, norepinephrine and epinephrine (collectively referred to as catecholamines) into neurons. This unique ability among the MAO inhibitors prevents the “cheese effect,” a dangerous hypertensive reaction caused by neural uptake of tyramine from tyramine-containing foods like aged cheeses, certain wines, yeast, beans, chicken liver and herring. Eldepryl exhibits no significant cheese effect at therapeutic dosages, and only minimal effects at extremely high dosages.

Eldepryl is a drug that was discovered around 1964-65. It was originally developed as a “psychic energizer,” designed to integrate some amphetamine-like brain effects with antidepressant effects. Also known as L-deprenyl, (-)-deprenyl, and selegiline, eldepryl has been intensively researched over the past 36 years - many hundreds of research papers on eldepryl have been published. Eldepryl has been shown to protect nerve cells against a wide (and growing) number of neurotoxins. Eldepryl has also been shown to be a “neuroprotection/ neurorescue agent” when nerve cells are exposed to damaging or stressful conditions.

4. Dosage Form: The dose of eldepryl will be different for different patients. Your doctor will determine the proper dose of eldepryl for you. Follow your doctor's orders or the directions on the label.

For the treatment of Parkinson's disease, the usual dose of eldepryl is 5 mg two times a day, taken with breakfast and lunch. Some patients may need less than this.

5. Drug Interactions: Eldepryl can interact with other medications such as Demerol, and many depression medications. Be sure to talk to your doctor about any other medication you are taking before taking eldepryl. Although eldepryl is less likely than non-selective monoamine oxidase inhibitors to interact with tyramine in food, like other monoamine oxidase inhibitors it can produce life-threatening reactions when given with pethidine. Zornberg GL, et al. severe adverse interaction between pethidine and eldepryl.

6. Pregnancy: Eldepryl has not been studied in pregnant women. However, this medicine has not been shown to cause birth defects or other problems in animal studies.

7. Nursing Mothers: is not known whether eldepryl passes into the breast milk.

8. Dietary and Alcohol Considerations: Alcoholic beverages or alcohol-free or reduced-alcohol beer and wine.
Foods that have a high tyramine content (most common in foods that are aged or fermented to increase their flavor), such as cheeses; fava or broad bean pods; yeast or meat extracts; smoked or pickled meat, poultry, or fish; fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; sauerkraut; or any overripe fruit. If a list of these foods and beverages is not given to you, ask your health care professional to provide one.

9. Possible Side Effects: Common side effects are nausea and vomiting. The most frequent side effects also include chest pain (severe); enlarged pupils; fast or slow heartbeat; headache (severe); increased sensitivity of eyes to light; increased sweating (possibly with fever or cold, clammy skin); nausea and vomiting (severe); stiff or sore neck.

10. Storage: Keep this medication in the container it came in, tightly closed, and out of reach of children. Eldepryl should be stored at below 30°C (86°F) and away from excess heat and moisture (not in the bathroom). Heat or moisture may cause the medicine to break down. Keep away from light. Talk to your pharmacist about the proper disposal of your medication. Throw away any medication that is outdated or no longer needed. Be sure that any discarded medicine is out of the reach of children.

11. Package Size and Type: Tablets: 5 mg, 10 mg.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov