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In Part I, we reviewed the theory, history, and overall pharmacology of l-deprenyl. Part II will discuss the possible applications of l-deprenyl, including its role as a neuroprotectant, antidepressant, and anti-addiction medication. But to continue where we left off last time is, as promised, let us first discuss l-deprenyl’s amphetamine metabolites.

Amphetamine Metabolites

L-deprenyl has three main metabolites: l-nordeprenyl, l-amphetamine, and l-methamphetamine, with nordeprenyl and l-methamphetamine being the most prominent (1). This is controversial because amphetamines (especially methamphetamine) are widely used drugs of abuse. Deprenyl even shares a similar discriminative stimulus with cocaine and amphetamine, although only at dosages that are above clinical relevance (9).

Furthermore, it is the d-amphetamines (and not the l- amphetamines) that are most often used recreationally. L-amphetamine and L-methamphetamine are approximately 10 times less potent at inhibiting the dopamine and norepinephrine re-uptake pumps compared to the d-isomers (2,3). L-methamphetamine requires a concentration of 4mg/kg in rats to elicit dopaminergic response. Concentrations of l-methamphetamine reach only .4mg/kg during a high dosage l-deprenyl regimen (10mg/kg compared to the therapeutic .25mg/kg [8]). The lack of potency of the l-amphetamines combined with the low dosage of deprenyl used clinically probably makes the abuse potential of l-deprenyl moot. Studies have failed to demonstrate l-deprenyl’s ability to maintain self-administration in animals at dosages even well above the therapeutic range (4).

The low dose amphetamines that are formed via metabolism might even have properties that contribute to l-deprenyl’s efficacy. Since patients on 10mg of l-deprenyl a day can excrete up to 7mg of l- (meth)amphetamine in 24 hours. Some authors have theorized that amphetamine metabolites are responsible for the beneficial effects of l-deprenyl treatment (5,6). In rats, inhibiting the formation of l-methamphetamine from l-deprenyl prevents acute behavioral effects such as increases in locomotor activity (7). L-amphetamine can increase EEG theta rhythms (which are associated with learning and memory) while d-amphetamine decreases them (10). Comparable with those derived from l-deprenyl therapy, low doses of l-amphetamine in rats can also prevent the age-related decline in learning ability (11).

L-methamphetamine’s role is more controversial given the neurotoxic potential of d-methamphetamine. High concentrations of l-methamphetamine can promote apoptosis (programmed cell death), but then again, so can high concentrations of l-deprenyl (12). At least one study found that l-methamphetamine prevented the neuroprotective actions of l-deprenyl (13). More encouraging is l-deprenyl’s ability to reduce the negative cardiovascular effects of d-methamphetamine use (14).

What conclusion can we draw from all of this? While metabolism of l-deprenyl into l-methamphetamine might potentially take away from some of the neuroprotective effects, the concentrations that are reached in the clinical situation are probably too low to cause much worry. Metabolism into l-amphetamine, on the other hand, has potential benefits for increasing cognition.

Those using l-deprenyl should be aware that treatment could cause a positive drug test for amphetamines. While an oral dose of 10mg is almost totally excreted within 24 hours (15), amphetamine metabolites can be found in the hair of l-deprenyl users for up to 4 weeks after a single oral dose (16). In an attempt to differentiate the urine content of therapeutic l-deprenyl use from methamphetamine abuse, Kim et al. found that the l-deprenyl users had a much higher ratio of amphetamine: methamphetamine in their urine (17). However, unforgiving and ethically flawed drug testing organizations are unlikely to pay attention to such a study. Thus, it’s probably best for athletes subject to drug testing to avoid l-deprenyl use.


The neuroprotective effect of l-deprenyl seen in Parkinson’s patients was originally thought to be related to MAO-B inhibition. By preventing the breakdown of dopamine, l-deprenyl can increase dopaminergic tone as well as prevent the formation of free radicals. However, it soon became apparent that much of l-deprenyl’s neuroprotective effect had nothing to do with MAO-B inhibition. L-deprenyl can protect DNA from the oxidizing effects of peroxynitrite even in neuronal cells that only contain MAO-A (18). MPTP is metabolized by MAO-B into MPP+, a dopaminergic toxin. Even when MPP+ is administered directly, deprenyl is still neuroprotective, proving that MAO-B inhibition is not a requirement (19). Lastly, deprenyl’s neuroprotection is not limited to dopaminergic neurons, but also noradrenergic (34) and cholinergic neurons (35).

The mechanism behind such effective neuroprotection lies in deprenyl’s upregulation of important antioxidant enzymes, such as superoxide dismutase (21). By increasing antioxidant enzymes, L-deprenyl, as well as its metabolite L-nordeprenyl, protects neurons from excitotoxicity and glutathione depletion (20). L-deprenyl also enhances nerve growth factor and reduces neuronal apoptosis (22,23).


The ultimate benefit of increasing antioxidant enzymes and reducing things like neuronal apoptosis is a longer, healthier life. L-deprenyl has been documented to increase the life expectancy of both rats (24) and dogs (25). In humans, l-deprenyl at dosages of 5-10mg per day can increase the life expectancy of Parkinson’s patients when combined with L-dopa (26). However, l-deprenyl’s longevity enhancing properties were questioned when another study demonstrated a slight excess in mortality rate in Parkinson’s patients taking the drug (27). A 2000 study published in Neurology failed to corroborate this excess mortality, reporting no significant difference in mortality between l-deprenyl and other Parkinson’s drugs (28).

Immunostimulant Effects

L-deprenyl’s life-extension effects are particularly noticeable in immunosuppressed animals (29,30). Besides upregulating antioxidant enzymes involved in immunity, deprenyl increases cytokine synthesis, particularly IL-1beta and IL-6 (31). It also enhances other immunofactors such as interferone-gamma, tumor necrosis factor alpha, and natural killer cells (33). L-deprenyl also has an anti-tumor effect in mammary cancer in rats (32). The anti-tumor effect is attributed to two mechanisms: 1. Increases in dopamine, which normalizes prolactin secretion (prolactin encourages the growth of mammary tumors) 2. Increases in norepinephrine in the spleen, which leads to the production of immunofactors.

Memory, Alzheimer’s and ADHD

L-deprenyl has been found to improve memory in both animals and humans. Improvements in spatial short-term memory have been noted in old dogs (36) and male rats (37). In female rats, l-deprenyl had a synergistic effect with estradiol in increasing spatial learning, also demonstrating a significant effect on its own (38). In humans, l-deprenyl improves memory in Alzheimer’s dementia (39) and can also aid in recovery from stroke (40).

In a trial comparing 5-10mg/day of l-deprenyl to 1mg/kg methylphenidate (Ritalin) in children with attention deficit hyperactivity disorder (ADHD), the l-deprenyl group experienced similar improvements in ADHD parameters with fewer side effects and drop-outs (41). A similar study found l-deprenyl effective in treating both children with ADHD and Tourette’s syndrome (42).

Sexual Function

Given the intimate relationship between dopamine and sexual function, l-deprenyl can act as an aphrodisiac in male rats (62), turning sexually low performing rats into high performing ones (63). Male rats on l-deprenyl also experience increased erectile potency (64) probably due to enhancement of nitric oxide, which can dilate blood vessels (65).

Hypersexuality is not uncommon in Parkinson’s patients receiving l-deprenyl and other dopaminergic drugs (66), and there is at least one case of a patient on l-deprenyl who developed transvestic fetishism (67). The man’s impulse to wear women’s clothing ceased when the drug was discontinued.


Atypical Drugs for Atypical Depression

The atypical subtype of major depressive disorder is defined by mood reactivity, interpersonal/rejection sensitivity, overeating, oversleeping, and leaden paralysis (a heavy feeling in the muscles). Atypical depression has also been called “neurotic depression” or “non-endogenous depression”, as the patient’s mood and symptoms are responsive temporarily to external factors (59). L-deprenyl has particular relevance to atypical depression, as atypical patients respond better to MAOIs than other antidepressants (60). Even moderate dosages of l-deprenyl in the range of 10-20mg/day have been shown to relieve atypical depressive symptoms in 59% of patients (61).

MAO-B, Stress and Cigarettes

While l-deprenyl’s neuroprotective effects do not rely on its ability to inhibit MAO-B, its antidepressant effects probably do. Why? Recently, the quest for the “true” antidepressant mechanism has shifted towards investigating the effects of hormones on the brain—particularly cortisol (43). It has been demonstrated that dexamethasone, a cortisol derivative, can increase the activity of MAO-B (44). We can infer that depressed individuals or others with high levels of stress hormones will display increased activity of MAO-B and subsequently lower dopamine and trace amine concentrations. This might partially explain the popularity of MAO-B inhibition by cigarette smoke in highly stressed people. Obviously, low dose l-deprenyl is a much healthier way to get the same effect.

Unfortunately, MAO-B inhibition by itself isn’t enough to treat most depressions. L-deprenyl at a dose of 10mg/day is not significantly better than placebo in relieving depressive symptoms (45). A more effective approach is exploiting deprenyl induced MAO-B inhibition and supplementing with phenylethylamine (PEA) or PEA precursors. Depressed subjects usually exhibit low levels of PEA. Deprenyl can be used to potentiate the effects of oral PEA that would not usually be bioavailible. When deprenyl is administered along with PEA, a rapid antidepressant response ensues, on par with that of amphetamine but without tolerance (46). Substantial antidepressant effect is even seen when deprenyl is combined with l-phenylalanine, which is enzymatically converted to PEA via the enzyme L-Amino Acid Decarboxylase (47).

It appears that in most cases, inhibition of both MAO-B and MAO-A is needed for an antidepressant response, as L-deprenyl is the most consistent and effective when administered at dosages of 30-60mg/day (48,49). At these dosages, it is likely that MAO-A is (at least partially) inhibited and dietary precautions would be necessary. What’s interesting about the 30mg/day dose is that no tyramine interactions were noted, suggesting that l-deprenyl even in non-selective dosages might have benefits over other MAOIs.

A particularly intriguing combination for depression is a MAO-B selective dose of l-deprenyl combined with the reversible MAO-A inhibitor moclobemide. Since neither of these drugs provokes the tyramine reaction, one can inhibit both MAO-A and MAO-B without following a low-tyramine diet. This combination has been found effective in treating Parkinson’s patients with depression (50).

MAO-B selective dosages of l-deprenyl can also potentiate the antidepressant effect of the serotonin precursor, 5-HTP (51). Since this is case, can a low dose of l-deprenyl be used to augment other antidepressants? In theory, yes. In reality, it’s a little risky.

The rationale for l-deprenyl augmentation is sound. By inhibiting MAO-B, there is increased availability of neurotransmitters and trace amines. Also, the “catecholamine enhancing” effect of l-deprenyl, along with the low doses of amphetamine metabolites would probably be useful in treating depression as well. Furthermore, l-deprenyl has been found to increase imipramine binding sites and downregulate central beta-adrenergic receptors, two markers of effective antidepressant treatment (52). So what’s the problem?

Besides the tyramine reaction, another problem with MAOIs is serotonin syndrome, particularly when combined with serotonin re-uptake inhibitors. Since MAO-B is not responsible for the deamination of serotonin, l-deprenyl should be theoretically safe with an SSRI. However, the results have been fatal at least once when fluoxetine was combined with l-deprenyl (53). This was probably due to the mild MAO-A and MAO-B inhibiting effects of fluoxetine (54,55). In other instances, fluoxetine and l-deprenyl were combined safely (56.57). “Cleaner” SSRI’s that lack MAOI properties such as sertraline might be better in combination with l-deprenyl. However, caution should still be taken and a conservative dose of l-deprenyl used (2.5-5mg/day) in order to prevent possible MAO-A “spillover.”

L-deprenyl is safest when used with antidepressants that do not block the serotonin transporter. These include bupropion, trazodone, reboxetine, and the tricyclics (58). Within the tricyclic category, greater caution should be taken with imipramine and clomipramine due to their higher affinity for the serotonin transporter.

L-Deprenyl and Addiction

While l-deprenyl itself probably has little abuse potential in humans at therapeutic dosages, some have theorized that because it inhibits the breakdown of dopamine, and drugs of abuse often work through dopaminergic pathways, then l-deprenyl can increase the abuse liability of other drugs (68). In rats, chronic low dose l-deprenyl treatment can potentiate cocaine-induced increases in dopamine (69). Other studies with humans have failed to find any significant interaction between cocaine and l-deprenyl in terms of the reported “high” (70).

There’s even evidence that deprenyl has anti-addictive properties. In humans, 7 days of continuous deprenyl therapy at 10mg/day reduces the subjective euphoria of cocaine by 40% and prevented the decrease in glucose utilization that normally accompanies cocaine administration (71). Memory circuits in the hippocampus can trigger memories of drug euphoria and cause cocaine relapse (72). Deprenyl normalization of brain metabolism can interfere with these conditioned memory responses. In this case, deprenyl’s nootropic and anti-addictive qualities are one in the same. The possibility of a relation between drug addiction and lapses in cognitive function is intriguing. By becoming “smarter” (at least biochemically by normalizing cerebral glucose metabolism), we simultaneously lower addictive potential. In a related study, a combination of piracetam and gingko biloba was ineffective at treating cocaine dependence (73). However, the role of nootropics in an overall treatment for addiction should not be ignored.

Besides being possibly effective for cocaine addiction, there is direct evidence that l-deprenyl can aid in smoking cessation. 10mg of l-deprenyl combined with a nicotine patch was found to be more effective than the patch alone (74). Similarly, in another study, 10mg of l-deprenyl was found to decrease cravings for cigarettes during abstinence as well as decrease the satisfaction received from cigarettes (75). The MAO-B inhibition of cigarette smoke is probably responsible for some of its pleasurable effects (76). Not only will l-deprenyl inhibit MAO-B without the unhealthy effects of cigarettes, its antioxidant activity could be especially beneficial to smokers and ex-smokers.

L-deprenyl has also been shown to preserve dopaminergic function during withdrawal from opiates (77). While l-deprenyl presents a promising adjunct to drug addiction therapy, controlled studies are definitely lacking.

Finding the Right Dose

Dosages of l-deprenyl will vary depending upon the reason for use. In general, low dosages (1-5mg/day) are best for neuroprotective, antioxidant, and life extension purposes. Moderate MAO-B selective dosages (5-15mg) are better suited for mild depression, ADHD, and general dopaminergic enhancement. Dosages higher than 15mg are only probably applicable to more serious depressive episodes.

In terms of the right dosage for neuroprotection, Carrillo and colleagues have conducted several animal studies to determine the best deprenyl dosage in order to increase life span. The neuroprotective effect of deprenyl vs. deprenyl dosage is a bell-shaped curve, meaning that more is not necessarily better. High dosages of deprenyl in rats can reduce rather than increase antioxidant enzymes (78). In male mice, there is a need to reduce the dosage of l-deprenyl over time in order to maintain the antioxidant effect (79). Females on the other hand require a lower dose than males, which increases as they get older (80).

While converting from dosages in animals to dosages in humans is rather tricky, deprenyl’s creator Joseph Knoll has admitted that the 10mg dose used in Parkinson’s is probably excessive for providing neuroprotection. Knoll himself (who is probably well into his 70s or beyond and still publishes multiple papers a year) takes 1mg a day (81).

According to Knoll, it is the post-developmental phase of life when deprenyl is most useful. Increased action of sex hormones with the onset of sexual maturity coincides with a dampening of monoamine activity enhancement (82). Thus, deprenyl is probably most useful after the completion of puberty in humans. Using the animal data from Carrillo et al, we can make some educated guesses on the dosages needed for life-extension and neuroprotection. Males in their 20s would probably benefit most from a dose of 2.5-5mg/day, while males above 30 probably don’t need more than 2.5mg per day. With females, dosages should start lower (2.5mg or less in the 20s) and increase slightly (up to 5mg/day) overtime. In females, estrogen probably works synergistically with l-deprenyl to provide neuroprotection (38). Females on birth control probably need an even lower dose due to pharmacokinetic interactions (83).

Enhancing an Enhancer Drug

There are many compounds that can have positive synergistic (or at least additive) effects when combined with l-deprenyl. Already mentioned have been l-dopa (Parkinson’s), PEA (depression), l-phenylalanine (depression), and estradiol (spatial learning). Melatonin acts synergistically with l-deprenyl to protect against MPTP toxicity (84). Both Vitamin E (86) and lipoic acid (85) have been studied either combined or head to head with deprenyl without any statistical benefit in measurements of Parkinson’s and life-extension. The acetylcholinesterase inhibitor tacrine showed increased effectiveness when combined with l-deprenyl in an animal model of Alzheimer’s disease (87).

Beyond L-deprenyl

Since the development of l-deprenyl in the 1960s, Joseph Knoll and researchers have made breakthroughs in propargylamine pharmacology and the science of neuroprotection, monoamine enhancement and life-extension. Venturing away from phenylethylamines and into tryptamines, Knoll and colleagues developed R- (-)-1-(benzofuran-2-yl)-2-propylaminopentane (BPAP), which appears 130 times more potent than l-deprenyl in measures of catecholamine (and serotonin) enhancement and neuroprotective benefits (88,89). Because prevailing medical practice dictates that we treat rather than prevent, drugs like BPAP may be slow to reach the public. For now, l-deprenyl represents a unique and effective option for not only those suffering from various illnesses, but also those just wishing to live a longer, healthier life.


Special thanks goes to David Pearce, author of The Good Drug Guide( and The Hedonistic Imperative ( His work has been an invaluable resource to me in writing these articles.


1. Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH. A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J Neural Transm. 2003 Nov;110(11):1241-55.

2. Ferris RM, Tang FL. Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-[3H]norepinephrine and [3H]dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus. J Pharmacol Exp Ther. 1979 Sep;210(3):422-

3. Yasar S, Bergman J. Amphetamine-like effect of l-deprenyl (selegiline) in drug discrimination studies. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):768-73.

4. Winger GD, Yasar S, Negus SS, Goldberg SR. Intravenous self-administration studies with l-deprenyl (selegiline) in monkeys. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):774-80.

5. Karoum F, Chuang LW, Eisler T, Calne DB, Liebowitz MR, Quitkin FM, Klein DF, Wyatt RJ. Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl’s therapeutic benefit: a biochemical assessment. Neurology. 1982 May;32(5):503-9.

6. Heinonen EH, Anttila MI, Lammintausta RA. Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):742-9.

7. Engberg G, Elebring T, Nissbrandt H. Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J Pharmacol Exp Ther. 1991 Nov;259(2):841-7.

8. Melega WP, Cho AK, Schmitz D, Kuczenski R, Segal DS. l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine. J Pharmacol Exp Ther. 1999 Feb;288(2):752-8.

9. Yasar S, Schindler CW, Thorndike EB, Szelenyi I, Goldberg SR. Evaluation of the stereoisomers of deprenyl for amphetamine-like discriminative stimulus effects in rats. J Pharmacol Exp Ther. 1993 Apr;265(1):1-6.

10. Nickel B, Borbe HO, Szelenyi I. Effect of selegiline and desmethyl-selegiline on cortical electric activity in rats. J Neural Transm Suppl. 1990;32:139-44.

11. Gelowitz DL, Richardson JS, Wishart TB, Yu PH, Lai CT.

12. Chronic L-deprenyl or L-amphetamine: equal cognitive enhancement, unequal MAO inhibition. Pharmacol Biochem Behav. 1994 Jan;47(1):41-5.

13. Szende B, Bokonyi G, Bocsi J, Keri G, Timar F, Magyar K. Anti-apoptotic and apoptotic action of (-)-deprenyl and its metabolites. J Neural Transm. 2001;108(1):25-33.

14. Am OB, Amit T, Youdim MB. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci Lett. 2004 Jan 30;355(3):169-72.

15. Schindler CW, Gilman JP, Graczyk Z, Wang G, Gee WL. Reduced cardiovascular effects of methamphetamine following treatment with selegiline. Drug Alcohol Depend. 2003 Nov 24;72(2):133-9.

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

17. Kronstrand R, Andersson MC, Ahlner J, Larson G. Incorporation of selegiline metabolites into hair after oral selegiline intake. J Anal Toxicol. 2001 Oct;25(7):594-601.

18. Kim EM, Chung HS, Lee KJ, Kim HJ. Determination of enantiomeric metabolites of l-deprenyl, d-methamphetamine, and racemic methamphetamine in urine by capillary electrophoresis: comparison of deprenyl use and methamphetamine use. J Anal Toxicol. 2000 May-Jun;24(4):238-44.

19. Maruyama W, Naoi M. Neuroprotection by (-)-deprenyl and related compounds. Mech Ageing Dev. 1999 Nov;111(2-3):189-200.

20. Wu RM, Chiueh CC, Pert A, Murphy DL Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo. Eur J Pharmacol. 1993 Oct 26;243(3):241-7.

21. Mytilineou C, Leonardi EK, Radcliffe P, Heinonen EH, Han SK, Werner P, Cohen G, Olanow CW. Deprenyl and desmethylselegiline protect mesencephalic neurons from toxicity induced by glutathione depletion. J Pharmacol Exp Ther. 1998 Feb;284(2):700-6.

22. Carrillo MC, Kanai S, Nokubo M, Ivy GO, Sato Y, Kitani K. (-)Deprenyl increases activities of superoxide dismutase and catalase in striatum but not in hippocampus: the sex and age-related differences in the optimal dose in the rat. Exp Neurol. 1992 Jun;116(3):286-94.

23. Semkova I, Wolz P, Schilling M, Krieglstein J. Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damage. Eur J Pharmacol. 1996 Nov 7;315(1):19-

24. Tatton WG, Chalmers-Redman RM. Modulation of gene expression rather than monoamine oxidase inhibition: (-)-deprenyl-related compounds in controlling neurodegeneration. Neurology. 1996 Dec;47(6 Suppl 3):S171-83.

25. Knoll J. The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl. Mech Ageing Dev. 1988 Dec;46(1-3):237-62.

26. Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44.

27. Birkmayer W, Knoll J, Riederer P, Youdim MB, Hars V, Marton J. Increased life expectancy resulting from addition of L-deprenyl to Madopar treatment in Parkinson’s disease: a longterm study. J Neural Transm. 1985;64(2):113-27.

28. Riggs JE. Deprenyl, excess mortality, and epidemiological traps. Clin Neuropharmacol. 1997 Jun;20(3):276-8.

29. Donnan PT, Steinke DT, Stubbings C, Davey PG, MacDonald TM. Selegiline and mortality in subjects with Parkinson’s disease: a longitudinal community study. Neurology. 2000 Dec 26;55(12):1785-9.

30. Freisleben HJ, Lehr F, Fuchs J. Lifespan of immunosuppressed NMRI-mice is increased by deprenyl. J Neural Transm Suppl. 1994;41:231-6.

31. Freisleben HJ, Neeb A, Lehr F, Ackermann H.
Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice. Arzneimittelforschung. 1997 Jun;47(6):776-80.

32. Muller T, Kuhn W, Kruger R, Przuntek H.
Selegiline as immunostimulant–a novel mechanism of action? J Neural Transm Suppl. 1998;52:321-8.

33. ThyagaRajan S, Felten SY, Felten DL. Antitumor effect of L-deprenyl in rats with carcinogen-induced mammary tumors. Cancer Lett. 1998 Jan 30;123(2):177-83.

34. Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC. 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. Mech Ageing Dev. 2002 Apr 30;123(8):1087-100.

35. Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langston JW. Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO B. Eur J Pharmacol. 1990 Aug 2;184(1):119-

36. Bronzetti E, Felici L, Ferrante F, Valsecchi B. Effect of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase-B-inhibitor L-deprenyl on the morphology of the rat hippocampus. Int J Tissue React. 1992;14(4):175-81.

37. Head E, Hartley J, Kameka AM, Mehta R, Ivy GO, Ruehl WW, Milgram NW. The effects of L-deprenyl on spatial short term memory in young and aged dogs. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Apr;20(3):515-30.

38. Bickford PC, Adams CE, Boyson SJ, Curella P, Gerhardt GA, Heron C, Ivy GO, Lin AM, Murphy MP, Poth K,

39. Wallace DR, Young DA, Zahniser NR, Rose GM. Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function. Neurobiol Aging. 1997 May-Jun;18(3):309-18.

40. Kiray M, Uysal N, Sonmez A, Acikgoz O, Gonenc S. Positive effects of deprenyl and estradiol on spatial memory and oxidant stress in aged female rat brains. Neurosci Lett. 2004 Jan 16;354(3):225-8.

41. Finali G, Piccirilli M, Oliani C, Piccinin GL. Alzheimer-type dementia and verbal memory performances: influence of selegiline therapy. Ital J Neurol Sci. 1992 Mar;13(2):141-8.

42. Sivenius J, Sarasoja T, Aaltonen H, Heinonen E, Kilkku O, Reinikainen K. Selegiline treatment facilitates recovery after stroke. Neurorehabil Neural Repair. 2001;15(3):183-90.

vAkhondzadeh S, Tavakolian R, Davari-Ashtiani R, Arabgol F, Amini H. Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):841-5.

vFeigin A, Kurlan R, McDermott MP, Beach J, Dimitsopulos T, Brower CA, Chapieski L, Trinidad K, Como P,

43. Jankovic J. A controlled trial of deprenyl in children with Tourette’s syndrome and attention deficit hyperactivity disorder. Neurology. 1996 Apr;46(4):965-8.

44. Pariante CM, Thomas SA, Lovestone S, Makoff A, Kerwin RW. Do antidepressants regulate how cortisol affects the brain? Psychoneuroendocrinology. 2004 May;29(4):423-47.

45. Carlo P, Violani E, Del Rio M, Olasmaa M, Santagati S, Maggi A, Picotti GB. Monoamine oxidase B expression is selectively regulated by dexamethasone in cultured rat astrocytes. Brain Res. 1996 Mar 4;711(1-2):175-

46. Mann JJ, Aarons SF, Wilner PJ, Keilp JG, Sweeney JA, Pearlstein T, Frances AJ, Kocsis JH, Brown RP.
A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor. Arch Gen Psychiatry. 1989 Jan;46(1):45-50.

47. Sabelli H, Fink P, Fawcett J, Tom C. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996 Spring;8(2):168-71.

48. Birkmayer W, Riederer P, Linauer W, Knoll J. L-deprenyl plus L-phenylalanine in the treatment of depression. J Neural Transm. 1984;59(1):81-7.

49. Sunderland T, Cohen RM, Molchan S, Lawlor BA, Mellow AM, Newhouse PA, Tariot PN, Mueller EA, Murphy

50. DL. controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor. Arch Gen Psychiatry. 1989 Jan;46(1):45-50.

51. Sunderland T, Cohen RM, Molchan S, Lawlor BA, Mellow AM, Newhouse PA, Tariot PN, Mueller EA, Murphy DL. High-dose selegiline in treatment-resistant older depressive patients. Arch Gen Psychiatry. 1994 Aug;51(8):607-15.

52. Steur EN, Ballering LA. Moclobemide and selegeline in the treatment of depression in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997 Oct;63(4):547.

53. L-deprenyl can potentiate the antidepressant response of 5-HTP at doses which cause near or total MAO-B inhibition. Mendlewicz J, Youdim MB. Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness. J Affect Disord. 1980 Jun;2(2):137-46.

54. Zsilla G, Barbaccia ML, Gandolfi O, Knoll J, Costa E. (-)-Deprenyl a selective MAO “B’ inhibitor, increases [3H]imipramine binding and decreases beta-adrenergic receptor function. Eur J Pharmacol. 1983 Apr 22;89(1-2):111-7.

55. Bilbao Garay J, Mesa Plaza N, Castilla Castellano V, Dhimes Tejada P. [Serotonin syndrome: report of a fatal case and review of the literature] Rev Clin Esp. 2002 Apr;202(4):209-11.

56. Mukherjee J, Yang ZY. Monoamine oxidase A inhibition by fluoxetine: an in vitro and in vivo study. Synapse. 1999 Mar 15;31(4):285-9.

57. Mukherjee J, Yang ZY.
Evaluation of monoamine oxidase B inhibition by fluoxetine (Prozac): an in vitro and in vivo study. Eur J Pharmacol. 1997 Oct 15;337(1):111-4.

58. Patel SV, Tariot PN, Asnis J. L-Deprenyl augmentation of fluoxetine in a patient with Huntington’s disease. Ann Clin Psychiatry. 1996 Mar;8(1):23-6.

59. Waters CH. Fluoxetine and selegiline–lack of significant interaction. Can J Neurol Sci. 1994 Aug;21(3):259-61.

60. Ritter JL, Alexander B. Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. Ann Clin Psychiatry. 1997 Mar;9(1):7-13.

61. Benazzi F. Can only reversed vegetative symptoms define atypical depression? Eur Arch Psychiatry Clin Neurosci. 2002 Dec;252(6):288-93.

62. Quitkin FM, Stewart JW, McGrath PJ, Tricamo E, Rabkin JG, Ocepek-Welikson K, Nunes E, Harrison W, Klein DF.

63. Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry Suppl. 1993 Sep;(21):30-4.

64. Quitkin FM, Liebowitz MR, Stewart JW, McGrath PJ, Harrison W, Rabkin JG, Markowitz J, Davies SO. l-Deprenyl in atypical depressives. Arch Gen Psychiatry. 1984 Aug;41(8):777-81.

65. Dallo J, Yen TT, Knoll J. The aphrodisiac effect of (-)deprenyl in male rats. Acta Physiol Hung. 1990;75 Suppl:75-6.

66. Knoll J, Yen TT, Miklya I. Sexually low performing male rats die earlier than their high performing peers and (-)deprenyl treatment eliminates this difference. Life Sci. 1994;54(15):1047-57.

67. Allard J, Bernabe J, Derdinger F, Alexandre L, McKenna K, Giuliano F. Selegiline enhances erectile activity induced by dopamine injection in the paraventricular nucleus of the hypothalamus in anesthetized rats. Int J Impot Res. 2002 Dec;14(6):518-22.

68. Thomas T, McLendon C, Thomas G. L-deprenyl: nitric oxide production and dilation of cerebral blood vessels. Neuroreport. 1998 Aug 3;9(11):2595-600.

69. Uitti RJ, Tanner CM, Rajput AH, Goetz CG, Klawans HL, Thiessen B.
Hypersexuality with antiparkinsonian therapy. Clin Neuropharmacol. 1989 Oct;12(5):375-83.

70. Riley DE. Reversible transvestic fetishism in a man with Parkinson’s disease treated with selegiline. Clin Neuropharmacol. 2002 Jul-Aug;25(4):234-7.

71. Schneider LS, Tariot PN, Goldstein B. Therapy with l-deprenyl (selegiline) and relation to abuse liability. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):750-6.

72. Schiffer WK, Azmoodeh M, Gerasimov M, Volkow ND, Fowler JS, Dewey SL. Selegiline potentiates cocaine-induced increases in rodent nucleus accumbens dopamine. Synapse. 2003 Apr;48(1):35-8.

73. Haberny KA, Walsh SL, Ginn DH, Wilkins JN, Garner JE, Setoda D, Bigelow GE. Absence of acute cocaine interactions with the MAO-B inhibitor selegiline. Drug Alcohol Depend. 1995 Jul;39(1):55-62.

74. Bartzokis G, Beckson M, Newton T, Mandelkern M, Mintz J, Foster JA, Ling W, Bridge TP. Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria. Neuropsychopharmacology. 1999 Jun;20(6):582-90.

75. White NM. Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction. 1996 Jul;91(7):921-49; discussion 951-65.

76. Kampman K, Majewska MD, Tourian K, Dackis C, Cornish J, Poole S, O’Brien C. A pilot trial of piracetam and ginkgo biloba for the treatment of cocaine dependence. Addict Behav. 2003 Apr;28(3):437-48.

77. Biberman R, Neumann R, Katzir I, Gerber Y. A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation. Addiction. 2003 Oct;98(10):1403-7.

78. Houtsmuller EJ, Thornton JA, Stitzer ML. Effects of selegiline (L-deprenyl) during smoking and short-term abstinence. Psychopharmacology (Berl). 2002 Sep;163(2):213-20. Epub 2002 Jul 13.

79. Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Shea C, Schlyer D, Wolf AP,

80. Warner D, Zezulkova I, Cilento R.
Inhibition of monoamine oxidase B in the brains of smokers. Nature. 1996 Feb 22;379(6567):733-6.

81. Grasing K, Ghosh S. Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal. Neuropharmacology. 1998 Aug;37(8):1007-17.

82. Carrillo MC, Kanai S, Kitani K, Ivy GO. A high dose of long term treatment with deprenyl loses its effect on antioxidant enzyme activities as well as on survivals of Fischer-344 rats. Life Sci. 2000 Oct 13;67(21):2539-48.

83. Carrillo MC, Kitani K, Kanai S, Sato Y, Ivy GO, Miyasaka K. 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 Sci. 1996;59(13):1047-57.

84. Carrillo MC, Kanai S, Sato Y, Nokubo M, Ivy GO, Kitani K. The optimal dosage of (-)deprenyl for increasing superoxide dismutase activities in several brain regions decreases with age in male Fischer 344 rats. Life Sci. 1993;52(24):1925-34.

85. Healy, D. The Psychopharmacologists III. Oxford University Press, Inc: New York. 2000. pp. 81-110.

86. Knoll J, Miklya I, Knoll B, Dallo J. Sexual hormones terminate in the rat: the significantly enhanced catecholaminergic/serotoninergic tone in the brain characteristic to the post-weaning period. Life Sci. 2000 Jul 7;67(7):765-73.

87. Laine K, Anttila M, Helminen A, Karnani H, Huupponen R. Dose linearity study of selegiline pharmacokinetics after oral administration: evidence for strong drug interaction with female sex steroids. Br J Clin Pharmacol. 1999 Mar;47(3):249-54.

88. Khaldy H, Escames G, Leon J, Bikjdaouene L, Acuna-Castroviejo D. Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion. Neurobiol Aging. 2003 May-Jun;24(3):491-500.

89. Freisleben HJ, Neeb A, Lehr F, Ackermann H. Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice. Arzneimittelforschung. 1997 Jun;47(6):776-80.

90. The Parkinson’s Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1993 Jan 21;328(3):176-83.

91. Dringenberg HC, Laporte PP, Diavolitsis P. Increased effectiveness of tacrine by deprenyl co-treatment in rats: EEG and behavioral evidence. Neuroreport. 2000 Nov 9;11(16):3513-6.

92. Knoll J, Yoneda F, Knoll B, Ohde H, Miklya I. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain. Br J Pharmacol. 1999 Dec;128(8):1723-32.

93. Shimazu S, Tanigawa A, Sato N, Yoneda F, Hayashi K, Knoll J. Enhancer substances: selegiline and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] enhance the neurotrophic factor synthesis on cultured mouse astrocytes. Life Sci. 2003 May 2;72(24):2785-92.