Deprenyl

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DeprenylWhat is Deprenyl?

Deprenyl ((R)-N,a-dimethyl-N-2-propynylbenzeneethanamine) is more commonly known as selegiline and has been sold under the brand names Atapryl, Carbex, Eldepryl, Emsam, and Zelapar. It was first discovered in Hungary in the 1960s, where a group of scientists led by Dr. Jozsef Knoll, was attempting to synthesize a molecule with the structural features of an MAO inhibitor (MAOI) with the stimulating effects of amphetamine. Structurally, it is a methamphetamine derivative with a propargyl group attached to the nitrogen atom and belongs to the phenethylamine group of drugs.

How does it work?

There are 2 main mechanisms behind deprenyl’s actions: it enhances dopamine signaling and seems to enhance antioxidative pathways.

Deprenyl inhibits enzymes called monoamine oxidases (MAOs). It is a selective, irreversible inhibitor of the B form (MAO-B), but it also inhibits MAO-A at high doses. MAOs are the enzymes responsible for degrading the neurotransmitter dopamine; therefore, deprenyl increases the amount of dopamine available in the central nervous system (CNS). It has also been demonstrated to enhance dopamine release and prevents its uptake. Together, these effects facilitate dopaminergic transmission.

Besides the effects on dopamine signaling, it increases serum insulin-like growth factor I and enhances life expectancy in rodents. It also promotes neuronal growth factor (NGF) synthesis, increases expression of superoxide dismutase (SOD, an antioxidant protein), and protects against toxicity induced by glutathione depletion.

Deprenyl Benefits

Unfortunately, there are no studies of the long-term effects of deprenyl in healthy humans. However, it is considered to have anti-aging effects. Healthy individuals report that it enhances mental function, motivation, mood, and even libido.  It enhances memory in rat models and even increased their lifespan by approximately 5%.

Clinically, deprenyl is prescribed to Parkinson’s disease patients. It is typically given in conjunction with levodopa (L-dopa), a precursor for dopamine. This combination increases dopamine in 2 ways; L-dopa increases the levels in the CNS and deprenyl prevents their degradation. This compound has also been shown to be effective in treating global ischemia, Tourette syndrome, traumatic brain injury, and narcolepsy. In addition, the FDA approved Emsam (a transdermal patch formulation of deprenyl) for the treatment of depression in 2006.  Short-term studies in Alzheimer’s disease were promising, but long-term investigations have proven disappointing. However, deprenyl may be useful in ameliorating cognitive dysfunction in Alzheimer’s disease when taken in conjunction with donepezil, which inhibits cholinesterase.

Deprenyl Side Effects

Deprenyl may cause nausea, dizziness, lightheadedness, or fainting, especially when the regimen is started. Other side effects include restlessness, insomnia, or decreased appetite, which are attributable to the effect of deprenyl on dopamine signaling. These symptoms are usually mild and can be eliminated by adjusting the dosage or route of administration. Any of the following side effects should be reported to a doctor: severe headache, chest pain, and irregular heartbeat.

Brain Games

Deprenyl Dosage

Appropriate doses vary considerably; young woman typically require much lower doses than older men to appreciate the effects of deprenyl (e.g., 2.5 mg/day vs. 20 mg/day). Doses above 20 mg/day are not suggested because they can result in severely elevated blood pressure due to nonspecific MAO-A inhibition that occurs at high doses. It is also important to consider that deprenyl binds to and inhibits MAO-B irreversibly. This means that the effects persist for a long time, because new MAO-B needs to be synthesized by the cell.

Deprenyl may be administered orally, through a patch, or via a dissolving tablet or droplets (buccally). People taking large doses of deprenyl should consider limiting their consumption of foods that contain tyramine (e.g., pickled or smoked foods, cheese, tofu), because this molecule is broken down by MAO-As, which may be inhibited by high doses of deprenyl.

Deprenyl is lipid-soluble, and bioavailability increases when oral doses are taken with high-fat food (20% vs. 4.4% under fasting conditions). Bioavailability is considerably higher (10-20 fold) in women that take oral contraceptive, and they may want to consider lower doses.

 

Bibliography

Ebadi, M., H. Brown-Borg, J. Ren, S. Sharma, S. Shavali, H. El ReFaey, and E. C. Carlson. “Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases.” Curr Drug Targets 7.11 (2006): 1513-529. Print.

Kitani, Kenichi, Setsuko Kanai, Maria Cristina Carrillo, and Gwen O. Ivy. “Deprenyl Increases the Life Span as Well as Activities of Superoxide Dismutase and Catalase but Not of Glutathione Peroxidase in Selective Brain Regions in Fischer Rats.” Annals of the New York Academy of Sciences 717.1 (1994): 60-71. Print.

Laine, Kari, Markku Anttila, Antti Helminen, Hari Karnani, and Risto Huupponen. “Dose Linearity Study of Selegiline Pharmacokinetics after Oral Administration: Evidence for Strong Drug Interaction with Female Sex Steroids.” British Journal of Clinical Pharmacology 47.3 (1999): 249-54. Print.

“Selegiline – PubMed Health.” PubMed Health. NIH, 16 Mar. 2011. Web. 06 Jan. 2012. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001015/>.

Tsunekawa, H., Y. Noda, A. Mouri, F. Yoneda, and T. Nabeshima. “Synergistic Effects of Selegiline and Donepezil on Cognitive Impairment Induced by Amyloid Beta (25–35).” Behavioural Brain Research 190.2 (2008): 224-32. Print.

Ukraintseva, Svetlana V., Konstantin G. Arbeev, Anatoly I. Michalsky, and Anatoly I. Yashin. “Antiaging Treatments Have Been Legally Prescribed for Approximately Thirty Years.” Annals of the New York Academy of Sciences 1019.1 (2004): 64-69. Print.

Wilcock, G. K., J. Birks, A. Whitehead, and Sir John Grimley Evans. “The Effect of Selegiline in the Treatment of People with Alzheimer’s Disease: A Meta-analysis of Published Trials.” International Journal of Geriatric Psychiatry 17.2 (2002): 175-83. Print.

 

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