16 replies to this topic

[luv2increase]

I thought it necessary to show the scientific evidence that selegiline aka deprenyl is safe and efficacious in humans. All of the following studies deal with selegiline and human beings except for one which shows selegiline rids the cognitive impairment caused from excessive iron levels in the rat brain.

There were many studies on selegiline; way too many to list here. There are a total of 2,323 on selegiline in the pubmed.gov National Institutes of Health database. In reality, there are many more than that!

As you will see evidenced through some of these studies, the benefits of selegiline are achieved without needing levels high enough to inhibit MAO-b. This shows that low dosages of 1mg every day to maybe even a couple times a week can exhibit positive results.

Through my research, I've failed to find any negative information on selegiline in healthy individuals. I hope you all find these studies of interest and will help you decide on whether or not to add selegiline to your regimen.

NOTE: For those of you not too familiar with reading these abstracts, the meat of them is at the end where it says "RESULTS" or "CONCLUSION".

I also have to do this is three posts.


http://www.ncbi.nlm....Pubmed_RVDocSum

1: Br J Cancer. 2003 Nov 17;89(10):1979-86.Click here to read Links
Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.
Seymour CB, Mothersill C, Mooney R, Moriarty M, Tipton KF.

Radiation and Environmental Science Centre, Dublin Institute of Technology, Kevin St, Dublin 8, Ireland.

l-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.

PMID: 14612913 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Clin Ter. 2002 Nov-Dec;153(6):377-80.Links
[Effectiveness and tolerability of selegiline in the treatment of pathological cerebral involutions]
[Article in Italian]

Bettini R, Gorini M.

Ospedale di Circolo, Università degli Studi dell'Insubria, Varese, Italia.

A dysfunction of dopaminergic systems with reduction of active dopamine, is well-known in cerebral involution. Twenty patients with mild-moderate pathological cerebral involution of atrophic and/or vascular origin, were treated with Selegiline (L-deprenyl), a monoamino-oxidase B inhibitor (10 mg/die for six months). Compared with a control group, Selegiline treated patients showed a statistically significant improvement in cognitive and behaviour capacities. At the end of investigation, "Mini Mental State" showed an improvement of 26.5% in Selegiline group and of 3.7% in control group (P < 0.01). "Echelle Clinique d'Aptitudes Intellectuelles" showed an improvement of 29.4% and of 10.8% respectively (P < 0.01). Selegiline treatment has shortened significantly the reaction times and has improved mnesic capacities. No side effects were observed during the study.

PMID: 12645393 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Neural Transm. 2003 May;110(5):509-15.Click here to read Links
Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B.
Tatton W, Chalmers-Redman R, Tatton N.

Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. william.tatton@mssm.edu

Deprenyl and other propargylamines are clinically beneficial in Parkinson's disease (PD). The benefits were thought to depend on monoamine oxidase B (MAO-B) inhibition. A large body of research has now shown that the propargylamines increase neuronal survival independently of MAO-B inhibition by interfering with apoptosis signaling pathways. The propargylamines bind to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The GAPDH binding is associated with decreased synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH but increased synthesis of anti-apoptotic proteins like BCL-2, Cu-Zn superoxide dismutase and heat shock protein 70. Anti-apoptotic propargylamines that do not inhibit MAO-B are now in PD clinical trial.

PMID: 12721812 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Life Sci. 2006 Aug 8;79(11):1034-9. Epub 2006 Apr 19.Click here to read Links
Cytoprotective effect of two synthetic enhancer substances, (-)-BPAP and (-)-deprenyl, on human brain capillary endothelial cells and rat PC12 cells.
Denes L, Szilágyi G, Gál A, Bori Z, Nagy Z.

Department of Vascular Neurology, Semmelweis University, Budapest, Hungary. denes42@opni.hu

Enhancer regulation is a new control mechanism in the brain [Knoll, J., 2003. Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives. Neurochemical Research 28(8), 1275-1297]. Enhancer substances exert their effect in bi-modal form with a highly characteristic dose-dependency. Two bell-shaped concentration curves have been published. The one in ultra low concentration range (fM) specific form of enhancer regulation and the other at high concentration (100 microM) non-specific form of enhancer regulation. Catecholaminergic neurons proved to be enhancer-sensitive cells. Since rat PC12 cells and human brain endothelial cells (HBEC) work under catecholaminergic influence, it was reasonable to expect that both the specific and non-specific form of the enhancer regulation might be detectable in these cells. We tested this possibility on these cultured cells under normoxia and hypoxia-reoxygenation. After 1 h hypoxia produced by Argon gas and 0, 2, 4, and 20 h reoxygenation the cell loss was calculated by propidiumiodide assay and the cell activity was investigated by Alamar Blue assay colorimetric measurement. The percentages of living and necrotic cells were expressed after propidiumiodide staining. Broad scale concentrations of the two compounds (1 fM-100 microM) were added to the culture strait after the oxygen deprivation. (-)-BPAP and (-)-deprenyl, due to their enhancer effect, exerted a significant cytoprotective effect on both HBECs and PC12 cells. In harmony with Knoll's publications we were able to demonstrate by the aid of (-)-BPAP and (-)-deprenyl that both HBEC and PC12 are enhancer-sensitive cells. We detected the specific form of the enhancer regulation in the ultra low concentration range (fM-pM) and also the non-specific form of the enhancer regulation was visible (mM-microM).

PMID: 16624331 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Biochem Biophys Res Commun. 2006 Jan 20;339(3):915-22. Epub 2005 Nov 28.Click here to read Links
Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins.
Nakaso K, Nakamura C, Sato H, Imamura K, Takeshima T, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago 683-8504, Japan. kazuhiro@grape.med.tottori-u.ac.jp

Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, gammaGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD.

PMID: 16325767 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Neurochem Int. 2008 Aug 30. [Epub ahead of print]Click here to read Links
1-Methyl-4-phenyl-pyridinium ion-induced oxidative stress, c-Jun phosphorylation and DNA fragmentation factor-45 cleavage in SK-N-SH cells are averted by selegiline.
Chetsawang B, Kooncumchoo P, Govitrapong P, Ebadi M.

Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakhonpathom 73170, Thailand; Department of Pharmacology, University of North Dakota, Grand Forks, ND 58203, USA; Department of Clinical Neuroscience, University of North Dakota, Grand Forks, ND 58203, USA.

Parkinson's disease is a progressive neurodegenerative disorder, associated with the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Recent studies have shown that c-Jun-N terminal kinase pathways might be involved in the oxidative stress-induced neuronal demise. In addition, there are several studies demonstrating that selegiline protects neural cell degeneration. In view of the above, the toxic effects of MPP(+) and the protective roles of selegiline were studied in cultures of human neuroblastoma (SK-N-SH) cell lines in the present study. MPP(+) significantly decreased cell viability but increased reactive oxygen species formation and lipid peroxidation, and the said effects were attenuated by selegiline. MPP(+) did not change the total levels of c-Jun but enhanced phosphorylation of c-Jun at Ser73 and cleavage of DNA fragmentation factor 45, which were diminished by selegiline. MPP(+)-treated SK-N-SH cells exhibited an irregularly shaped nuclear chromatin or DNA fragmentation, which was abolished by selegiline. These data suggest that c-Jun-N terminal kinase pathways are involved in oxidative stress-induced dopaminergic neuronal degeneration and pretreatment with selegiline affords neuroprotection by inhibiting these cell death-signaling pathways.

PMID: 18805449 [PubMed - as supplied by publisher]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Orv Hetil. 2006 Jul 9;147(27):1251-7.Links
[Molecular mechanisms of the neuroprotective effect of (-)-deprenyl]
[Article in Hungarian]

Pálfi M, Szökó E, Kálmán M.

Magyar Tudományos Akadémia, Neurokémiai Kutatócsoport, Budapest. melinda.palfi@net.sote.hu

(-)-Deprenyl, the irreversible inhibitor of monoamine oxidase B, has been used for decades in the therapy of Parkinson's disease. It improves parkinsonian symptoms due to its dopamine potentiating and antioxidant properties and presumedly delays disease progression. Its complex pharmacological action cannot be explained solely by its monoamine oxidase B inhibitory property. Recently, (-)-deprenyl has been demonstrated to exert antiapoptotic, neuroprotective effects on a number of in vitro and in vivo models in a dose significantly lower than required for monoamine oxidase B inhibition. (-)-Deprenyl and related propargylamines prevent apoptotic cell death by preserving the integrity of the mitochondrion that may be based on the activation of a complex transcriptional program. The changes in gene expression initiated by propargylamines incited to search for further possible target molecules that would explain more accurately the antiapoptotic effect of these compounds. The latest molecular targets include such classical metabolic enzymes, the homologues of which may participate in the regulation of gene expression as a part of transcriptional factor complexes. Some of the propargylamine targets--glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, nuclear amine oxidases--have already been demonstrated to be capable of transforming the metabolic changes in the cell to transcriptional responses. Data are accumulating about the relationship of these enzymes and propargyl compounds, but the real significance of this issue will only be established by future research.

PMID: 16927880 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Child Adolesc Psychopharmacol. 2004 Fall;14(3):418-25.Click here to read Links
Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial.
Mohammadi MR, Ghanizadeh A, Alaghband-Rad J, Tehranidoost M, Mesgarpour B, Soori H.

Department of Psychiatry, Tehran University of Medical Sciences, Psychiatry and Clinical Psychology Research Center, Roozbeh Hospital, Tehran, Iran.

OBJECTIVES: The aim of this study was to examine the selegiline treatment compared to methylphenidate (MPH) in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: Forty subjects, aged 6-15 years, boys and girls, who were diagnosed as having ADHD, using the criteria of the Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV), were randomly assigned to receive either selegiline or MPH for 60 days. Treatment outcomes were assessed using the Attention Deficit Hyperactivity Scale (ADHS) administered at baseline and on days 14, 28, 42, and 60 following the commencement of treatment. Side effects were also rated. RESULTS: There were no significant differences between sex, age, weight, and ethnicity of participants in the 2 groups. Both groups showed a significant improvement over the 60 days of treatment resulting from the teachers' and parents' ADHS scores across the treatment. CONCLUSION: Following the trial, MPH did not effect greater mean improvement as a result of the parents' or teachers' ADHS scores than selegiline. Thus, selegiline appears to be effective and well tolerated for ADHD in children and adolescents.

PMID: 15650498 [PubMed - indexed for MEDLINE]

Edited by luv2increase, 03 October 2008 - 11:32 PM.

[luv2increase]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Child Adolesc Psychopharmacol. 2006 Aug;16(4):404-15.Click here to read Links
Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder.
Rubinstein S, Malone MA, Roberts W, Logan WJ.

Division of Neurology, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, Ontario, Canada.

There is evidence suggesting a role for dopamine in attention-deficit/hyperactivity disorder (ADHD). Pharmacological treatments that act on the dopamine system have been successful in reducing ADHD symptoms. However, unlike traditional stimulants (i.e., methylphenidate), selegiline is a monoamine oxidase inhibitor (MAOI) that has been shown to reduce ADHD symptoms without producing undesirable side effects. In this study using a randomized, double- blind, placebo-controlled, crossover design, cognitive tasks and behavioral rating scales were administered to measure the effectiveness of selegiline in treating different symptoms of ADHD in 11 children aged 6-13. Results indicate that selegiline may target specific symptoms of ADHD including: sustained attention, the learning of novel information, hyperactivity, and peer interactions. Because the drug was not associated with negative side effects and did not specifically reduce symptoms of impulsivity, selegiline may be a preferred treatment for individuals who present with the primarily inattentive subtype of ADHD.

PMID: 16958566 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Curr Drug Targets. 2006 Nov;7(11):1513-29.Click here to read Links
Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases.
Ebadi M, Brown-Borg H, Ren J, Sharma S, Shavali S, El ReFaey H, Carlson EC.

Department of Pharmacology, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58203, USA. mebadi@medicine.nodak.edu

Selegiline inhibits the activity of monoamine oxidase B, enhances the release of dopamine, blocks the uptake of dopamine, acts as a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. It possesses cognition-enhancing functions, rejuvenates serum insulin-like growth factor I in aged rats, and enhances life expectancy in rodents. Selegiline possesses neurotrophic-like actions, and rescues axotomized motorneurons independent of monoamine oxidase B inhibition. It enhances the synthesis of nerve growth factor, protects dopaminergic neurons from glutamate-mediated neurotoxicity, and protects dopaminergic neurons from toxic factors present in the spinal fluid of parkinsonian patients, and the said effect may be mediated via elaborating brain derived neurotrophic factor. Selegiline increases the striatal superoxide dismutase, protects against peroxynitrite- and nitric oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by glutathione depletion. It stimulates the biosynthesis of interleukin 1-beta and interleukin-6, is an immunoenhancing substance, possesses antiapoptotic actions, and is neuroprotectant in nature. Selegiline has been shown to be efficacious in Parkinson's disease, global ischemia, Gille de la Tourette syndrome, and narcolepsy. Its therapeutic efficacy in Alzheimer's disease remains uncertain. In Alzheimer's disease, short term studies of selegiline suggest a beneficial effect; whereas long term studies are less convincing.

PMID: 17100591 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Affect Disord. 2008 Jan;105(1-3):15-23. Epub 2007 Jun 13.Click here to read Links
The selegiline transdermal system in major depressive disorder: a systematic review of safety and tolerability.
Robinson DS, Amsterdam JD.

Worldwide Drug Development, 102 East Avenue, Burlington, VT 05401, United States. dsrobmd@aol.com

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are highly efficacious antidepressants, but safety concerns have limited their broad use. METHODS: We reviewed key safety and tolerability data from all clinical trials of patients with major depressive disorder (MDD) accrued during the clinical development of the selegiline transdermal system (STS), as reported to the Food and Drug Administration. This review includes data from both controlled and uncontrolled clinical trials involving STS-treated (n=2036) and placebo-treated (n=668) patients. RESULTS: Except for the initial trial, subsequent trials, which involved STS doses ranging from 3 mg/24 h to 12 mg/24 h, lacked tyramine restrictions, and no acute hypertensive reactions occurred during study treatment. Safety experience with STS 6 mg/24 h supports this therapeutic dose without tyramine dietary modifications, but until more data are available for STS doses 9 mg/24 h and 12 mg/24 h, foods that are rich sources of tyramine should be avoided. The principal side effects of STS therapy were local dermal reactions and insomnia, both of which were dose-related. Side effects associated with MAOI treatment, such as sexual dysfunction and excessive weight gain, were uncommon. CONCLUSIONS: A comprehensive review of safety from the clinical development program suggests that the STS is safe and well tolerated, with an improved safety margin compared with orally administered MAOIs.

PMID: 17568687 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Clin Pharmacol. 2007 Oct;47(10):1256-67. Epub 2007 Aug 22.Click here to read Links
Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules.
Azzaro AJ, Ziemniak J, Kemper E, Campbell BJ, VanDenBerg C.

Somerset Pharmaceuticals Inc., Tampa, FL, USA. ajazzaro@aol.com

The selegiline transdermal system is a monoamine oxidase inhibitor that was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. The current study was conducted during the selegiline transdermal system development program to characterize the single-dose pharmacokinetics and absolute bioavailability of selegiline administered by the 6-mg/24-h selegiline transdermal system in healthy volunteers. Selegiline transdermal system results were compared with those obtained after a single 10-mg oral dose of selegiline HCl. The selegiline pharmacokinetics differed greatly between the 2 routes of administration. Transdermal selegiline administration reduced metabolism and produced a high, sustained plasma selegiline concentration over the dosing period, with an absolute bioavailability of 73%. By contrast, oral dosing produced a sharp plasma selegiline peak that occurred within 1 hour and declined rapidly, with an absolute bioavailability of 4%. The data provide the basis for therapeutic advantages of the selegiline transdermal system in administering antidepressant doses of selegiline.

PMID: 17715422 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Orv Hetil. 2008 Feb 17;149(7):305-15.Click here to read Links
[Role of apoptosis in the kidney after reperfusion]
[Article in Hungarian]

Toronyi E.

Semmelweis Egyetem, Altalános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest Baross u. 23. 1082. toronyi@trans.sote.hu

Organ transplantation is one of the most important achievements of medicine in the 20th century. Ischaemia-reperfusion has a great impact on both: immediate organ function and long-term survival. Organ transplantation can be regarded as a clinical model of ischaemia-reperfusion phenomenon. AIM: The prevention of ischaemia-reperfusion damages. Apoptosis plays a key-role in these processes. METHODS: Apoptosis was investigated in the course of human kidney transplantation. In animal experiments the characteristics of apoptosis were analysed after short ischaemia. Calcium antagonists: verapamil, nifedipine, bepridil, fendiline and (-)-deprenyl, an irreversible selective inhibitor of monoamino oxidase type B, (-)-deprenyl, were administered to prevent apoptosis. RESULTS: The observations showed that in the course of human kidney transplantation necrotic, apoptotic and proliferating renal tubular cells can be observed. All calcium channel blockers and (-)-deprenyl decreased the occurrence and degree of apoptosis in rat kidney. CONCLUSIONS: The functional capacity of tubular cells is a significant factor in the adequate kidney function. The reduction of the apoptosis of tubular cells possibly could improve the function of transplanted kidneys.

PMID: 18258561 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Exp Neurol. 2005 Nov;196(1):177-83. Epub 2005 Aug 24.Click here to read Links
Selegiline protects against recognition memory impairment induced by neonatal iron treatment.
de Lima MN, Laranja DC, Caldana F, Grazziotin MM, Garcia VA, Dal-Pizzol F, Bromberg E, Schröder N.

Programa de Pós-Graduação em Gerontologia Biomédica, Instituto de Geriatria e Gerontologia, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, 90619-900 Porto Alegre, RS, Brazil.

Excess of iron in the brain has been implicated in the pathogenesis of several human neurodegenerative diseases, for example Alzheimer's disease and Parkinson's disease. It has been shown that the neonatal period is critical for the establishment of normal iron content in the adult brain. Moreover, it is known that aging alters the cerebral distribution of this metal. We have recently described that neonatal administration of iron severely impaired novel object recognition memory in rats. The aim of the present study was to determine whether selegiline, a monoamine oxidase (MAO) inhibitor known for its neuroprotective properties, could protect rats against cognitive impairment induced by neonatal administration of iron. In the first experiment, male Wistar rats received vehicle (5% sorbitol in water) or iron (10.0 mg/kg) orally from postnatal days 12 to 14 and saline (0.9% NaCl) or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting 24 h before the first iron dosing. In the second experiment, rats were given either vehicle or iron (10.0 mg/kg) orally from postnatal days 12 to 14 followed by saline or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting when rats reached adulthood (50th day after birth). Iron-treated rats given selegiline in both doses showed no deficits in recognition memory. Rats receiving iron but no selegiline presented memory deficits. This is the first study reporting the reversion of iron-induced memory impairment, supporting the view that our model can be considered as a useful tool in the search for new drugs with neuroprotective and/or memory enhancing properties.

PMID: 16122736 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Neurol Res. 2008 May;30(4):417-9. Epub 2008 Jan 30.Links
Selegiline reduces cisplatin-induced neuronal death in neuroblastoma cells.
Müller T, Przuntek H, Rieks M, Mackowiak A.

Department of Neurology, St Josef Hospital, University of Bochum, Gudrunstr. 56, 44791 Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de

Long-term administration of the monoamine oxidase (MAO)-B inhibitor selegiline may reduce neuronal death based on preclinical findings and reduce progression of chronic neurodegeneration due to outcomes of long-term clinical trials in patients with Parkinson's disease. Additional modes of action of this compound are immune system modulating and neurotrophic properties. We investigated the impact of simultaneous selegiline and cisplatin administration on the degree of cisplatin-induced cell death in SH-SY 5Y human neuroblastoma cells. We found a significantly reduced cell death rate after 50 and 74 hours after 2 hours lasting cisplatin exposure of SH-SY 5Y cells with additional selegiline treatment in comparison with cultures without selegiline. No previous incubation of cell cultures with selegiline was necessary to achieve this neuroprotective effect. We suggest that the neuroprotective effect of selegiline is predominantly associated with neurotrophic actions but not MAO-B inhibition, because SH-SY 5Y human neuroblastoma cells only contain MAO-A. Clinically, our findings support an early start of long-term treatment with selegiline in view of the various neurotoxin hypotheses and mechanisms of neuronal death in chronic neurodegenerative disorders.

PMID: 18237459 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Neurocytol. 2003 May;32(4):329-43.Click here to read Links
Neuroprotective actions of Selegiline in inhibiting 1-methyl, 4-phenyl, pyridinium ion (MPP+)-induced apoptosis in SK-N-SH neurons.
Sharma SK, Carlson EC, Ebadi M.

Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, North Dakota, USA. skumar@medicine.nodak.edu

We have examined mitochondrial membranes and molecular hallmarks of apoptosis in response to increasing concentrations of 1-Methyl, 4-phenyl, Pyridinium ion (MPP(+)) in SK-N-SH neurons and have evaluated the neuroprotective potential of Selegiline with a primary objective to explore its mechanism(s) of neuroprotection. MPP(+)-induced apoptosis was characterized by spherical appearance, suppressed neuritogenesis, phosphatidyl serine externalization, plasma membrane perforations, mitochondrial membrane potential (Delta Psi) collapse, mitochondrial aggregation, and nuclear DNA fragmentation and condensation. At lower concentrations, MPP(+) (10-100 microM) produced mitochondrial swelling and loss of cristae, and at higher concentrations (300-500 microM), degeneration and aggregation of mitochondrial membranes in the peri-nuclear region, which were attenuated by Selegiline (10-50 microM) pre-treatment. At still higher concentrations, MPP(+) (>500 microM) produced necrotic changes represented by mitochondrial and plasma membrane ballooning and perforations. Selegiline provided partial neuroprotection at higher concentrations of MPP(+). MPP(+)-induced increases in reactive oxygen species, lipid peroxidation, cytochrome-C release, necrosis factor kappa-B (NF-kappa-B) activation, 8-hydroxy, 2 deoxy guanosine synthesis, alpha-synuclein indices, and reductions in glutathione, ATP, and superoxide dismutase were attenuated by Selegiline. Selegiline also attenuated MPP(+)-induced transcriptional activation of c-fos, c-jun, GAPDH, and caspase-3, suggesting that it may provide neuroprotection by preserving mitochondrial membranes, by attenuating molecular markers of apoptosis, by scavenging free radicals, and by regulating immediate early genes involved in neurodegeneration.

PMID: 14724376 [PubMed - indexed for MEDLINE]

[luv2increase]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Ann N Y Acad Sci. 2004 Jun;1019:64-9.Click here to read Links
Antiaging treatments have been legally prescribed for approximately thirty years.
Ukraintseva SV, Arbeev KG, Michalsky AI, Yashin AI.

Max Planck Institute for Demographic Research, 18057 Rostock, Germany. ukraintseva@cds.duke.edu

There is an interesting divergence between the achievements of geriatrics and gerontology. On the one hand, during the last 30 years physicians in many developed countries have successfully prescribed several medicines to cure various symptoms of senescence. On the other hand, the influence of such medicines on human life span practically has not been studied. The most common of the relevant medicines are nootropic piracetam, gamma-aminobutyric acid (GABA), selegiline, Ginkgo biloba, pentoxifylline, cerebrolysin, solcoseryl, ergoloid, vinpocetin, sertraline, and estrogens, among others. Available data from human clinical practices and experimental animal studies indicate that treatments with these drugs improve learning, memory, brain metabolism, and capacity. Some of these drugs increase tolerance to various stresses such as oxygen deficit and exercise, stimulate the regeneration of neurons in the old brain, and speed up the performance of mental and physical tasks. This means that modern medicine already has "antiaging" treatments at its disposal. However, the influence of such treatments on the mean and maximal life span of humans, and on the age trajectory of a human survival curve has been poorly studied. The increase in human life expectancy at birth in the second half of the last century was mostly caused by the better survival at the old and oldest old rather than at the young ages. In parallel, the consumption of brain protective and regenerative drugs has been expanding in the elderly population. We provide evidence in support of the idea that the consumption of medicines exerting antiaging properties may contribute to the increase in human longevity.

PMID: 15246996 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Neural Transm Suppl. 2006;(71):143-56.Links
Deprenyl: from chemical synthesis to neuroprotection.
Magyar K, Pálfi M, Jenei V, Szöko E.

Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. kalman.magyar@net.sote.hu

During the last decades (-)-deprenyl has become the golden standard of MAO-B inhibitors. It possesses dopamine potentiating and antioxidant properties; however, its effects cannot be explained solely by the enzyme inhibitory action. (-)-Deprenyl prevents the toxicity of certain selective neurotoxins and recently it was demonstrated to increase cell-cell adhesion as well. The complexity of its pharmacological effects reflects the action of both the parent compound and the active metabolites. (-)-Deprenyl and related propargylamines (DRPs) show neuroprotective features in a variety of in vitro and in vivo models that is dependent on the propargyl moiety. The main presumptive targets to date include glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, some kinase cascades, as well as pro- and antiapoptotic proteins, beside the inhibition of MAO-B. The antiapoptotic activity of DRPs converges upon the maintenance of mitochondrial integrity, due to the initiation of a complex transcriptional program, the details of which are yet to be elucidated.

PMID: 17447425 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Brain Inj. 2005 Feb;19(2):149-54.Links
Selegiline in the management of apathy following traumatic brain injury.
Newburn G, Newburn D.

Rotorua Rehabilitation Clinic, Rotorua, New Zealand. dengil@xtra.co.nz

PRIMARY OBJECTIVE: To provide a brief review of apathy following traumatic brain injury (TBI) and describe the use of selegiline in a group of patients with this symptom. MAIN OUTCOME: Four patients are described who showed improvement in Apathy Evaluation Scale scores and functional improvement, following the use of selegiline. In each case, selegiline was well tolerated whereas methylphenidate was not. CONCLUSIONS: Selegiline shows potential for the management of apathy following TBI. This provides further evidence that impaired dopaminergic processes are prominent in the genesis of these symptoms. However, these findings require confirmation in controlled studies.

PMID: 15841758 [PubMed - indexed for MEDLINE]

[niner]

luv2increase, are there any studies that look at safety in large numbers of young people, over a substantial length of time? It is very difficult to "prove" safety, or even demonstrate it, when the effects are either subtle or take a long time to manifest. Small or short studies are not capable of demonstrating safety in a case like this. Deprenyl is not the sort of compound that I would take lightly.

[luv2increase]

Deprenyl is not the sort of compound that I would take lightly.

What is your reasoning behind this?

[luv2increase]

luv2increase, are there any studies that look at safety in large numbers of young people, over a substantial length of time?

I would think that since selegiline is being investigated for treatment in children with ADHD and has already had two studies done with children which showed it has a better side-effect profile that even methylphenidate; it is pretty safe for those of all ages.


One could assume that in the following study the ages of the test subjects were that from all over the spectrum.

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Clin Psychopharmacol. 2006 Dec;26(6):579-86.Click here to read Links
Selegiline transdermal system in the prevention of relapse of major depressive disorder: a 52-week, double-blind, placebo-substitution, parallel-group clinical trial.
Amsterdam JD, Bodkin JA.

Depression Research Unit, Department of Psychiatry, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. jamsterd@mail.med.upenn.edu

The selegiline transdermal system (STS) is a monoamine oxidase inhibitor (MAOI) with unique pharmacokinetic and pharmacodynamic properties that was developed to overcome limitations of orally administered MAOIs, particularly dietary tyramine restrictions. We present data from a long-term study assessing the safety and efficacy of initial and continuation STS therapy in patients with major depressive disorder (MDD). After 10 weeks of treatment with STS 6 mg/24 h, 322 patients who responded with a 17-item Hamilton Depression Rating Scale score of 10 or less were randomly assigned to double-blind treatment with STS 6 mg/24 h or placebo for 52 weeks. Relapse was defined as meeting the following criteria on 2 consecutive visits: (1) 17-item Hamilton Depression Rating Scale score of 14 or more, (2) a Clinical Global Impression of Severity score of 3 or more with a 2-point increase from double-blind baseline, and (3) the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode. At study week 52, significantly fewer STS patients experienced relapse of major depressive episode (25/149 [16.8%]) compared with placebo (50/163 [30.7%]) (P = 0.0025). In addition, patients receiving STS experienced a significantly longer time to relapse compared with those receiving placebo (P = 0.0048). The safety profile of STS was similar to placebo, with the exception of application-site reactions (STS, 15.2%; placebo, 3.7%). No cases of hypertensive crisis were reported, despite the lack of requirement for dietary tyramine restrictions. In conclusion, STS was well tolerated and efficacious in maintaining a sustained response in MDD patients. The results of this study suggest that STS may be suitable in the long-term treatment of MDD.

PMID: 17110814 [PubMed - indexed for MEDLINE]

Here is another great study for you niner, and all others which may have doubts.

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Acta Neurol Scand Suppl. 1983;95:57-80.Links
Deprenyl (selegiline): the history of its development and pharmacological action.
Knoll J.

Deprenyl inhibits MAO-B selectively in different animal species and in man. Its safety margin is remarkable. We were able to block MAO-B activity in the brain selectively in vivo in four species (mouse, rat, cat, dog) with s.c. administration of 0.17-0.31% of LD50. The usual oral dose range in clinical practice, 5-20 mg daily (0.05-0.2 mg/kg), is about ten times lower than the orally active dose in the rat. Deprenyl proved to be safe drug in man. Neither hypertensive reactions nor the need for any special dietary care were ever encountered during long-term (2-8 years) daily administration of the drug. The most important effect of deprenyl in the brain is the sensitization of dopaminergic neurons to physiological and pharmacological influences, but in contrast to levodopa or bromocrytine, deprenyl does not elicit an acute increase in dopaminergic activity. The effect of deprenyl is due, on the one hand, to the inhibition of MAO-B and, on the other hand, to inhibition of the uptake of dopamine. In agreement with its peculiar spectrum of pharmacological activity, deprenyl proved to be a useful adjuvant to levodopa alone or in combination with a peripheral decarboxylase inhibitor. In addition, a supplement of deprenyl in Parkinson's disease led to significant prolongation of the duration of the illness. This has not been observed so far with other antiparkinsonian drugs. The dopamine content of the human caudate nucleus decreases by 13% per decade over the age of 45. The hypothesis has been put forward that the significant increase of incidence of depression in the elderly, the age-dependent decline in male sexual vigour and the frequent appearance of parkinsonian symptoms in the later decades of life might be attributed to a decrease of dopamine and 'trace amines' in the brain. The possibility of countering these biochemical lesions of ageing by long-term administration of deprenyl, a selective inhibitor of MAO-B which facilitates dopaminergic and 'trace-aminergic' activity in the brain, and is a safe drug in man, is considered in detail.

PMID: 6428148 [PubMed - indexed for MEDLINE]

Edited by luv2increase, 04 October 2008 - 02:10 AM.

[niner]

luv2increase, are there any studies that look at safety in large numbers of young people, over a substantial length of time?

I would think that since selegiline is being investigated for treatment in children with ADHD and has already had two studies done with children which showed it has a better side-effect profile that even methylphenidate; it is pretty safe for those of all ages.

That's a good sign, but it would still depend on dose and duration.

One could assume that in the following study the ages of the test subjects were that from all over the spectrum.

We could assume it, but it would be better to know.

http://www.ncbi.nlm....Pubmed_RVDocSum

1: J Clin Psychopharmacol. 2006 Dec;26(6):579-86.Click here to read Links
Selegiline transdermal system in the prevention of relapse of major depressive disorder: a 52-week, double-blind, placebo-substitution, parallel-group clinical trial.
[...]
The selegiline transdermal system (STS) is a monoamine oxidase inhibitor (MAOI) with unique pharmacokinetic and pharmacodynamic properties that was developed to overcome limitations of orally administered MAOIs, particularly dietary tyramine restrictions. We present data from a long-term study assessing the safety and efficacy of initial and continuation STS therapy in patients with major depressive disorder (MDD). After 10 weeks of treatment with STS 6 mg/24 h, 322 patients who responded with a 17-item Hamilton Depression Rating Scale score of 10 or less were randomly assigned to double-blind treatment with STS 6 mg/24 h or placebo for 52 weeks. Relapse was defined as meeting the following criteria on 2 consecutive visits: (1) 17-item Hamilton Depression Rating Scale score of 14 or more, (2) a Clinical Global Impression of Severity score of 3 or more with a 2-point increase from double-blind baseline, and (3) the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode. At study week 52, significantly fewer STS patients experienced relapse of major depressive episode (25/149 [16.8%]) compared with placebo (50/163 [30.7%]) (P = 0.0025). In addition, patients receiving STS experienced a significantly longer time to relapse compared with those receiving placebo (P = 0.0048). The safety profile of STS was similar to placebo, with the exception of application-site reactions (STS, 15.2%; placebo, 3.7%). No cases of hypertensive crisis were reported, despite the lack of requirement for dietary tyramine restrictions. In conclusion, STS was well tolerated and efficacious in maintaining a sustained response in MDD patients. The results of this study suggest that STS may be suitable in the long-term treatment of MDD.
PMID: 17110814

This looks pretty good. It was a transdermal study though, so that's pretty different than the pulse dosing that we would be using. Still, this is not too bad.

http://www.ncbi.nlm....Pubmed_RVDocSum

1: Acta Neurol Scand Suppl. 1983;95:57-80.Links
Deprenyl (selegiline): the history of its development and pharmacological action.
Knoll J.

Deprenyl inhibits MAO-B selectively in different animal species and in man. Its safety margin is remarkable. We were able to block MAO-B activity in the brain selectively in vivo in four species (mouse, rat, cat, dog) with s.c. administration of 0.17-0.31% of LD50. The usual oral dose range in clinical practice, 5-20 mg daily (0.05-0.2 mg/kg), is about ten times lower than the orally active dose in the rat. Deprenyl proved to be safe drug in man. Neither hypertensive reactions nor the need for any special dietary care were ever encountered during long-term (2-8 years) daily administration of the drug. The most important effect of deprenyl in the brain is the sensitization of dopaminergic neurons to physiological and pharmacological influences, but in contrast to levodopa or bromocrytine, deprenyl does not elicit an acute increase in dopaminergic activity. The effect of deprenyl is due, on the one hand, to the inhibition of MAO-B and, on the other hand, to inhibition of the uptake of dopamine. In agreement with its peculiar spectrum of pharmacological activity, deprenyl proved to be a useful adjuvant to levodopa alone or in combination with a peripheral decarboxylase inhibitor. In addition, a supplement of deprenyl in Parkinson's disease led to significant prolongation of the duration of the illness. This has not been observed so far with other antiparkinsonian drugs. The dopamine content of the human caudate nucleus decreases by 13% per decade over the age of 45. The hypothesis has been put forward that the significant increase of incidence of depression in the elderly, the age-dependent decline in male sexual vigour and the frequent appearance of parkinsonian symptoms in the later decades of life might be attributed to a decrease of dopamine and 'trace amines' in the brain. The possibility of countering these biochemical lesions of ageing by long-term administration of deprenyl, a selective inhibitor of MAO-B which facilitates dopaminergic and 'trace-aminergic' activity in the brain, and is a safe drug in man, is considered in detail.
PMID: 6428148

Knoll asserts that the drug is safe in man no less than three times, but he doesn't give any evidence to that effect, other than 'no hypertensive crisis' in some unknown number of patients, presumably greater than zero. It is, to be sure, just an abstract, but it wouldn't have been hard to mention the number of pts at least once. Knoll sounds like a deprenyl evangelist, so that makes me take this with a grain of salt. This is the first time I'd heard the 'male sexual vigor' angle; another boner pill? Those are always popular. Seriously though, this does sound like an interesting drug.

Deprenyl is not the sort of compound that I would take lightly.

What is your reasoning behind this?

It's a MAOI.

[zoolander]

Being a prescription medication used primarily with Parkinson's disease and depression means that you will find it hard to justify or find a study that looks at the long term effects of deprenyl supplementation in young healthy individuals.

In the absence of long term studies in the target population ask yourself the following questions

1. why would I use deprenyl?
2. are there any benefits for using deprenyl?
3. are there any risks with using deprenyl?

Decide whether to supplement.
Assess how capable you are to assess risk and benefit. Do you understand the science??
Accept full responsibility for your decision to use deprenyl for whetever off-label reason you decide (i.e cognitive enhancement).
Do your best to measure for risk and benefit both objectively and subjectively.

Edited by zoolander, 04 October 2008 - 03:11 AM.

[luv2increase]

It's a MAOI.

You have the negative stigma towards MAO-a inhibitors which affect serotonin and carry more risks. This is not the case for selegiline so try again.





You will find it hard to locate any study on virtually any drug that goes for an extended amount of time. Asking me to find this is almost an impossible task. Concluding from all this evidence thrown in your face niner, and you still being scared, I'd say that you shouldn't use supplements at all. There are virtually no supplements or whatever that has super long duration studies.


I've found nothing negative to selegiline's use. You are trying to use logic that atheists say Christians use to prove there is a god which is "Prove to me there is no god". It cannot be done. This situation is the complete inverse of that though. You have a monumental amount of evidence via sound scientific studies and their researches (people most likely smarter than you or I) which say that selegiline is extremely safe, and nothing saying the opposite. Concluding from this, it is very dumb to say "show me that it is safe" when that has already been done.

You say that it's an MAO-I. Well, it is a selective, irreversible MAO-b inhibitor at dosages under 10mg a day. It is considered the safest MAO-I there is. I want you to elaborate the MAO-I statement. I want to see what you come up with. I'll ask you like this; can you show me any information which proves there is an inherrant risk to taking any MAO-I?


Zoo, you talk about benefit vs risk. Can you elaborate on the risks so people can weigh the benefits to them? I sincerely can't see any risks when taking less than 10mg a day ONLY because more than 10mg a day will inhibit MAO-a also which then "I" would have to watch what I eat etc... because like while taking all MAO-a inhibitors, one must cut all food containing tyramine out of their diet. Thanks Zoo!

Edited by luv2increase, 04 October 2008 - 04:31 AM.

[M.speciosa]

It's a MAOI.

Can you elaborate on the risks so people can weigh the benefits to them? I sincerely can't see any risks when taking less than 10mg a day ONLY because more than 10mg a day will inhibit MAO-a also which then "I" would have to watch what I eat etc... because like while taking all MAO-a inhibitors, one must cut all food containing tyramine out of their diet. Thanks Zoo!

I just wanted to mention that even at doses higher than 10 mg, many people find that they can still eat whatever foods they want. I've been on 12 mg of Selegiline (Emsam) for quite a while now and I've never noticed any problems with certain tyramine-containing foods. As a matter of fact, I was on 18 mg for a couple weeks, and even then I still had no issues. Now, I'm certainly not saying that you won't have any dietary restrictions, but there is a good chance that you may not. I would follow the diet strictly at first, and then adjust accordingly (at doses >10 mg). Selegiline is one fantastic drug...a lifesaver in my case!

Edited by M.speciosa, 06 October 2008 - 05:15 AM.

[bran319]

It's a MAOI.

Can you elaborate on the risks so people can weigh the benefits to them? I sincerely can't see any risks when taking less than 10mg a day ONLY because more than 10mg a day will inhibit MAO-a also which then "I" would have to watch what I eat etc... because like while taking all MAO-a inhibitors, one must cut all food containing tyramine out of their diet. Thanks Zoo!

I just wanted to mention that even at doses higher than 10 mg, many people find that they can still eat whatever foods they want. I've been on 12 mg of Selegiline (Emsam) for quite a while now and I've never noticed any problems with certain tyramine-containing foods. As a matter of fact, I was on 18 mg for a couple weeks, and even then I still had no issues. Now, I'm certainly not saying that you won't have any dietary restrictions, but there is a good chance that you may not. I would follow the diet strictly at first, and then adjust accordingly (at doses >10 mg). Selegiline is one fantastic drug...a lifesaver in my case!

The transdermal delivery mediates the lack of dietary interaction. You are also getting far better absorption so the equivalent oral dose would be two to three times higher.

Again, just to repeat, transdermal delivery bypasses MAO-A inhibition in the gut and this is why tyramine is inactivated and you are not getting hypertensive. Oral doses of selegiline above 10mgs. have been shown to inhibit MAO-A in the gut and would put one at risk for a hypertensive reaction.

[edward]

Its all about dosage. IMO .5 to 1 mg per day is plenty for most people and I am not sure I buy the whole increase the dose with age. All of the rat studies that showed prolonged lifespan used a human equivalent of .25-1 mg per day for their entire lives anything more and there was no effect or a negative effect on lifespan.

Personally I use roughly .25 mg per day transdermal with a day off per week (my mandatory no supplement day). I cut a 6mg absorption equivalent EMSAM patch into 12 squares, stick one of these little squares (.5 mg) on every morning and take it off after dinner for roughly 12 hours of exposure = .25 mg. One prescription of EMSAM 30 patches lasts a ridiculous 360 + days. At first I was skeptical about the possibility of cutting the patches so small but the resulting 1.5/1cm rectanglish shapes are not that small and seem to adhere fine even after swimming or working out they stay on better than nicotine patches.

edit: and before you ask, yes you need a prescription and yes it will be difficult to get one but once you do you can't beat the price (especially with insurance) and convenience, no more ordering and wondering about quality, plus you can't beat the sustained drip of a patch.

Edited by edward, 07 October 2008 - 06:32 PM.

[M.speciosa]

It's a MAOI.

Can you elaborate on the risks so people can weigh the benefits to them? I sincerely can't see any risks when taking less than 10mg a day ONLY because more than 10mg a day will inhibit MAO-a also which then "I" would have to watch what I eat etc... because like while taking all MAO-a inhibitors, one must cut all food containing tyramine out of their diet. Thanks Zoo!

I just wanted to mention that even at doses higher than 10 mg, many people find that they can still eat whatever foods they want. I've been on 12 mg of Selegiline (Emsam) for quite a while now and I've never noticed any problems with certain tyramine-containing foods. As a matter of fact, I was on 18 mg for a couple weeks, and even then I still had no issues. Now, I'm certainly not saying that you won't have any dietary restrictions, but there is a good chance that you may not. I would follow the diet strictly at first, and then adjust accordingly (at doses >10 mg). Selegiline is one fantastic drug...a lifesaver in my case!

The transdermal delivery mediates the lack of dietary interaction. You are also getting far better absorption so the equivalent oral dose would be two to three times higher. Again, just to repeat, transdermal delivery bypasses MAO-A inhibition in the gut and this is why tyramine is inactivated and you are not getting hypertensive. Oral doses of selegiline above 10mgs. have been shown to inhibit MAO-A in the gut and would put one at risk for a hypertensive reaction.

As quoted below, they still are not sure about the dietary restriction thing with the transdermal patches. The quoted text below is taken from this PDF.

WHAT THE PHARMACIST SHOULD KNOW
Selegiline HCl is currently approved, without dietary
restrictions, at oral doses of 10 mg/day as an adjunct
to levodopa in the management of late-stage
Parkinson’s disease and has been shown to have
antidepressant activity at 30 to 60 mg/day. At these
doses, the selectivity for MAO-B is lost, resulting in
increased cardiovascular sensitivity to tyramine due to
MAO-A inhibition, necessitating dietary restriction. STS
has pharmacodynamic and pharmacokinetic
advantages over oral selegiline, leading to greater
CNS MAO-A and MAO-B inhibition and less inhibition
of intestinal and liver MAO-A. However, only the
lowest dose (6 mg/24 hr) has been shown to be safe
without the use of dietary restriction of foods rich in
tyramine. The recommended initial and target dose is
one 6 mg/24 hr patch daily. The only adverse effects
different from placebo included application site
reactions and lightheadedness due to a drop in blood
pressure.

WHAT YOU MAY NOT BE TOLD
The more limited data available for STS 9 mg/24 hr
and 12 mg/24 hr do not rule out food effects, so
patients receiving these higher doses should follow
dietary restrictions that advise them to avoid certain
foods or beverages. It is uncertain whether the 9 mg or
12 mg strengths are more effective than the 6 mg
strength. The only two major studies assessing
transdermal selegiline for the treatment of major
depressive disorder only took place for six to eight
weeks. There are no long-term randomized controlled
trials examining the safety and efficacy of the drug. WHAT THE PATIENT SHOULD KNOW
STS should be applied to dry, smooth skin on your
upper chest or back, upper thigh, or the outer surface
of the upper arm. Be sure to remove the old patch
before applying the new patch – wear only one patch
at a time. Change the patch at the same time everyday
while rotating patch sites to minimize the risk of
application site reactions. After applying the patch,
wash your hands. After removing the old patch, throw
it away out of the reach of children or pets. If you begin
to feel like your depression is getting worse or if you
begin to have suicidal thoughts, please contact your
physician immediately. Be sure to tell everyone
participating in your care all of your current
medications, and indicate that you are taking an MAO-
I. In addition, do not take any over-the-counter
medications or herbals that have a WARNING label
describing possible interactions with MAO-Is. It is
advisable to avoid foods and drinks with high tyramine
content, especially if you are taking the 9mg/24hr or 12
mg/24 hr patches. Consuming tyramine with an MAO-I
may lead to an unsafe increase in your blood
pressure. Additional information can be found at
http://www.bms.com/products/data/.

[edward]

As quoted below, they still are not sure about the dietary restriction thing with the transdermal patches.

True and I agree if you were to stick the whole 6 or 12 mg patch on (giving you both MAO A and B inhibition), but unless you are using selegiline for depression there is no need for such a huge dose, and it is counterproductive to life extension. Just look at the rat studies there is no need for anything remotely approaching MAO A inhibition levels for life extension and general brain health.

Cutting a 6mg patch into twelve .5 mg slips and then only wearing one 12-16 hrs or taking 1 mg sublingually, well you are not going to have to worry about MAO A or dietary issues.

[bran319]

M.Speciosa I just wanted it to be clear that you cannot extrapolate EMSAM dosages over to oral dosages. The distinction must be drawn for the reasons I listed above. STS (EMSAM) spares gut MAO-A thereby bypassing or greatly minimizing tyramine interactions. Oral dosing of selegiline above 10mgs. would not have this benefit and you run the risk of inhibiting MAO-A in the gut and having a tyramin pressor response.

Here is an overview if anyone is interested on MAO-A inhibitors and EMSAM pharmacokinetics:

http://www.cnsspectr...x?articleid=400

From the article:

"STS allows inhibition of brain MAO-A and MAO-B enzymes with reduced effects on GI MAO-A, thereby reducing the risk of possible interactions with tyramine-rich foods at therapeutic doses."

If you read the full article, you'll see that even the 30mg & 40mg patches are likely to not cause dietary problems, but that data from the test trials indicated that the most tyramine-sensitive patient could in theory have a hypertensive crisis at these doses if they ate a meal, very, very high in tyramine, which is probably why Somerset was OK with the dietary restrictions on labelling for the higher doses.

I just don't want a newb coming along, finding this thread on selegiline safety and assume he can take oral doses above 10mgs. and there is no risk.

Have a nice day.

[M.speciosa]

As quoted below, they still are not sure about the dietary restriction thing with the transdermal patches.

True and I agree if you were to stick the whole 6 or 12 mg patch on (giving you both MAO A and B inhibition), but unless you are using selegiline for depression there is no need for such a huge dose, and it is counterproductive to life extension. Just look at the rat studies there is no need for anything remotely approaching MAO A inhibition levels for life extension and general brain health.

Cutting a 6mg patch into twelve .5 mg slips and then only wearing one 12-16 hrs or taking 1 mg sublingually, well you are not going to have to worry about MAO A or dietary issues.

I agree, but I am prescribed Emsam for refractory depression, so thats why I take the high dose (12mg). Unfortunatley the Emsam doesn't quite work as well as I'd like for my depression. Although I must say, it certainly works better than anything else I've been on for depression (SSRIs, SNRI's, TCAs, etc.). Plus it doesn't even have close to as many side effects as the dreaded SSRIs . I would say the most positive aspect of the Emsam would be the increased energy levels and concentration. My doc may put me on another MAOI such as Nardil or Parnate. I'm assuming that those would have stronger MAO A inhibiting properties. My only concern is that the other MAOI's won't have the cognitive enhancing properties of Selegiline. Does anyone know if all the MAOI's have the cognitive enhancing properties like Selegiline?

I would love to see a chart or something, showing the "inhibition strength" of the different MAOI's. I'll see what I can find.

Edited by M.speciosa, 09 October 2008 - 01:07 AM.

[M.speciosa]

M.Speciosa I just wanted it to be clear that you cannot extrapolate EMSAM dosages over to oral dosages. The distinction must be drawn for the reasons I listed above. STS (EMSAM) spares gut MAO-A thereby bypassing or greatly minimizing tyramine interactions. Oral dosing of selegiline above 10mgs. would not have this benefit and you run the risk of inhibiting MAO-A in the gut and having a tyramin pressor response.

Here is an overview if anyone is interested on MAO-A inhibitors and EMSAM pharmacokinetics:

http://www.cnsspectr...x?articleid=400

From the article:

"STS allows inhibition of brain MAO-A and MAO-B enzymes with reduced effects on GI MAO-A, thereby reducing the risk of possible interactions with tyramine-rich foods at therapeutic doses."

If you read the full article, you'll see that even the 30mg & 40mg patches are likely to not cause dietary problems, but that data from the test trials indicated that the most tyramine-sensitive patient could in theory have a hypertensive crisis at these doses if they ate a meal, very, very high in tyramine, which is probably why Somerset was OK with the dietary restrictions on labelling for the higher doses.

I just don't want a newb coming along, finding this thread on selegiline safety and assume he can take oral doses above 10mgs. and there is no risk.

Have a nice day.

Interesting! That's new to me, thanks for the info!