Class: Monoamine Oxidase B Inhibitors
VA Class: CN500
Chemical Name: (R)-N,α-Dimethyl-N-2-propynyl-benzeneethanamine hydrochloride
Molecular Formula: C13H17N•ClH
CAS Number: 14611-52-0
Uses for Selegiline Hydrochloride
Used as adjunctive therapy for symptomatic treatment of parkinsonian syndrome in patients who exhibit a deteriorating response to levodopa/carbidopa; designated an orphan drug by FDA for this condition.1 2 4 5 6 7 8 34 35 36 37 38 39 40 65 66 85 92 93 Appears to be most beneficial when used during the early stages of the “wearing off” effect.6 7 36 38 49 Especially useful in improving “end-of-dose” motor fluctuations.5 6 7 49 51 85
Has been used as monotherapy in patients with newly diagnosed parkinsonian syndrome†.5 7 8 37 53 54 55 56 73 84 85 93 130 Because selegiline is well tolerated and possibly neuroprotective (i.e., reduces the rate of progression of parkinsonian syndrome3 5 8 53 54 55 56 57 58 59 60 130 ), some clinicians initiate therapy with selegiline in such patients, reserving levodopa or another agent (i.e., dopamine agonist) until manifestations become severe enough to warrant more aggressive therapy.8 11 57 65 122 130 However, the manufacturers state that there is no evidence from controlled studies indicating that selegiline provides benefit in the absence of concurrent levodopa therapy.1 2
Has been used with equivocal results for the palliative treatment of mild to moderate dementia of the Alzheimer’s type† (Alzheimer’s disease, presenile or senile dementia).61 62 63 104 105 106 107 127 128
Selegiline Hydrochloride Dosage and Administration
Concomitant Levodopa/Carbidopa Therapy
Available as selegiline hydrochloride; dosage expressed in terms of the salt.1
Maximum 10 mg daily.1 (See Risks Associated with MAO Inhibition under Cautions.)
No special population dosage recommendations.1
Cautions for Selegiline Hydrochloride
Risks Associated with MAO Inhibition
Selectivity for MAO-B is relative.1 2 3 At dosage of 10 mg daily, selegiline hydrochloride inhibits cerebral MAO-B while having little effect on MAO-A in the GI tract and liver.1 2 4 5 22 32 84 At high dosages (e.g., 30–40 mg daily), the selectivity usually diminishes and the drug will inhibit MAO-B and MAO-A.1 2 4 5 22 32
Hypertensive crises following ingestion of foods containing large amounts of tyramine (i.e., cheese reaction) have occurred in patients receiving nonselective MAO inhibitors.123 Hypertensive reactions reported rarely in patients receiving selegiline hydrochloride 10 mg daily (the maximum recommended dosage);1 at dosages >10 mg daily, the likelihood of hypertensive reactions increases.1 2 5 9 10 11 12 113 Use selegiline with caution regardless of the dosage.1 (See Interactions and also Advice to Patients.)
Concomitant use of highly serotonergic drugs (e.g., SSRIs, tricyclic antidepressants) and MAO inhibitors, including selegiline, is potentially hazardous and may result in serotonin syndrome.1 2 13 16 17 97 99 100 101 112 Manifestations may include mental status changes (e.g., agitations, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).1 126 131 133 Generally avoid concomitant use.1 2 (See Interactions.)
Because of the complexity of the MAO enzyme system, observe patients closely for atypical responses.1
Exacerbation of Levodopa-associated Adverse Effects
Selegiline may exacerbate levodopa-associated adverse effects (e.g., dyskinesias1 2 5 49 50 64 66 68 ), presumably by increasing dopaminergic activity; effects generally can be mitigated by reducing the levodopa dosage by 10–30%.1 2 5 68
Epidemiologic studies indicate patients with Parkinson’s disease have a twofold to approximately sixfold greater risk of developing melanoma than the general population.1 2 Unclear whether increased risk is due to Parkinson’s disease or other factors (e.g., drugs used to treat the disease).1 2
Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including selegiline).1 2 Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.1 2
Safety and efficacy not established.1
Safety and efficacy in geriatric patients not studied specifically to date; however, parkinsonian syndrome, for which safety and efficacy have been established, occurs principally in patients >50 years of age.1 2 4 5 6 7 8 34 35 36 37 38 39 40 53 54 55 56
Common Adverse Effects
Many of the adverse effects in patients receiving selegiline plus levodopa result from increased dopaminergic activity and can be mitigated by reducing levodopa dosage; these effects include exacerbation of dyskinesias, confusion, and hallucinations.1 2 5 49 50 64 66 67 68
Interactions for Selegiline Hydrochloride
The possibility of interactions such as those reported with nonselective MAO inhibitors should be considered.1
Interactions Involving Nonselective MAO Inhibitors
Hypertensive crises following ingestion of foods containing large amounts of tyramine (i.e., cheese reaction) have occurred in patients receiving nonselective MAO inhibitors.123
Concomitant use of highly serotonergic drugs and MAO inhibitors is potentially hazardous and may result in serotonin syndrome.1 2 13 16 17 97 99 100 101 112 (See Risks Associated with MAO Inhibition under Cautions.)
Specific Drugs and Foods
Drug or Food
Antidepressants, SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline)
Antidepressants, tricyclics (e.g., amitriptyline, protriptyline)
Consult specialized references on food constituents or a dietician for specific information on the tyramine content of foods and beverages122
MAO inhibitors, nonselective
Avoid concomitant use132
Stupor, muscular rigidity, severe agitation, and elevated temperature reported in some patients receiving meperidine with selegiline; resolution usually occurs over several days following discontinuance of both drugs1 2 5 19 20 112 118
Sympathomimetic agents (e.g., ephedrine)
Cold or hay fever preparations containing pressor agents (e.g., ephedrine) generally can be given to patients receiving selegiline hydrochloride dosages of ≤10 mg daily without undue risk of uncontrolled hypertension1 2 5
Selegiline Hydrochloride Pharmacokinetics
Following single oral 10-mg dose, peak plasma concentrations of the first-pass metabolites (l-desmethylselegiline, l-methamphetamine, and l-amphetamine) are 3- to 20-fold higher than the peak plasma concentrations of selegiline.1 108 110 At steady-state, peak plasma selegiline and metabolite concentrations are increased 2.6- to 4-fold and 1.5- to 2-fold, respectively, compared with values following a single dose.1 108
Following administration of a single 10-mg dose in a limited number of adults ≥60 years of age, systemic exposure was twice that reported in adults 18–30 years of age.1
Plasma Protein Binding
Extensively metabolized, principally in the gut wall and liver, to l-desmethylselegiline and l-methylamphetamine (CYP-mediated) and then to l-amphetamine.1 32 108 The amphetamine metabolites may be hydroxylated and then conjugated with glucuronic acid.5 32 88 108
l-Desmethylselegiline is an irreversible inhibitor of MAO-B,1 32 44 45 46 47 110 but its contribution to MAO-B inhibition during selegiline therapy may be only minor.110 The levorotatory amphetamine isomers are less potent CNS stimulants than the racemic or dextrorotatory isomers.5 26 44
Excreted principally in urine as conjugated and unconjugated metabolites1 5 12 26 27 28 29 30 31 32 44 (20–63% as l-methamphetamine, 9–26% as l-amphetamine, and 1% as l-desmethylselegiline5 12 31 44 ).
Capsules and Tablets
Relatively selective MAO-B inhibitor.1 2 3 At dosage of 10 mg daily, selegiline hydrochloride inhibits cerebral MAO-B while having little effect on MAO-A in the GI tract and liver.1 2 4 5 22 32 84 At high dosages (e.g., 30–40 mg daily), the selectivity usually diminishes and the drug will inhibit MAO-B and MAO-A.1 2 4 5 22 32
Principal physiologic action in the management of parkinsonian syndrome is irreversible inhibition of MAO-B within the nigrostriatal pathways in the CNS,1 2 4 5 22 thereby blocking microsomal metabolism of dopamine 1 2 4 5 22 and enhancing dopaminergic activity in the substantia nigra.1 2 4 5 22 Reduces the amount of levodopa required to maintain optimum dopamine concentrations in the brain of patients with parkinsonian syndrome.1 2 4 5 22
Prevents MAO-B mediated production of the neurotoxin methyl-4-phenylpyridinium ion (MPP+) from phenyl-1,2,3,6-tetrahydropyridine (MPTP).4 5 83 84 If an MPTP-like substance contributes to the pathogenesis of parkinsonian syndrome, the inhibition of oxidation of such a substance may protect against its neurotoxic effects.4 5 83 84
The ability to promote neuronal survival and neurite outgrowth and release of dopamine from intact neurons and also to block activation of N-methyl-d-aspartate (NMDA)-sensitive glutamate receptors may contribute to selegiline’s activity.1 2 4 5 22 23 43 78 79 80 81 82 83 84 85
Advice to Patients
Advise patient that serious adverse reactions (e.g., hypertensive reactions) rarely have occurred even at the recommended dosage when tyramine-containing foods or a sympathomimetic drug was used concomitantly.1 2 122 Importance of avoiding foods and beverages with a high tyramine content, particularly if dosage >10 mg daily is used.5 9 10 12 32
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Selegiline Hydrochloride Capsules
Selegiline Hydrochloride Tablets
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Date published: July 01, 2004
Last reviewed: April 19, 2012
Date modified: February 08, 2016
1. Somerset Pharmaceuticals, Inc. Eldepryl (selegiline hydrochloride) capsules prescribing information. Morgantown, WV; 2011 Aug.
2. Mylan Pharmaceuticals Inc. Selegiline hydrochloride tablets, USP, prescribing information. Morgantown, WV; 2009 Nov.
3. Fleeger CA, ed. USAN 1994: USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1994:497.
4. Knoll J. Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand. 1983; 95(Suppl):57-80.
5. Chrisp P, Mammen GJ, Sorkin EM. Selegiline: a review of its pharmacology, symptomatic benefits and protective potential in Parkinson’s disease. Drugs Aging. 1991; 1:228-48. [PubMed 1794016]
6. Golbe LI, Langston JW, Shoulson I. Selegiline and Parkinson’s disease: protective and symptomatic considerations. Drugs. 1990; 39:646-51. [PubMed 2112994]
7. Fuller MA, Tolbert SR. Selegiline: initial or adjunctive therapy of Parkinson’s disease? DICP Ann Pharmacother. 1991; 25:36-40.
8. Anon. Drugs for Parkinson’s disease. Med Lett Drugs Ther. 1993; 35:31-4. [PubMed 8096322]
9. Prasad A, Glover V, Goodwin BL et al. Enhanced pressor sensitivity to oral tyramine challenge following high dose selegiline treatment. Psychopharmacology. 1988; 95:540-3. [PubMed 3145523]
10. McGrath PJ, Stewart JW, Quitkin FM. A possiblel-deprenyl induced hypersensitive reaction. J Clin Psychopharmacol. 1989; 9:310-1. [IDIS 257463] [PubMed 2504782]
11. Ahlskog JE. Treatment of Parkinson’s disease. Postgrad Med. 1994; 95:52-69. [IDIS 328348] [PubMed 8153048]
12. Schulz R, Antonin KH, Hoffmann E et al. Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther. 1989; 46:528-36. [IDIS 260992] [PubMed 2510962]
13. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol. 1993; 31:603-30. [IDIS 323333] [PubMed 8254702]
14. Suchowersky O, deVries J. Possible interactions between deprenyl and Prozac. Can J Neurol Sci. 1990; 17:352-3. [PubMed 2119870]
15. Jermain DM, Hughes PL, Follender AB. Potential fluoxetine–selegiline interaction. Ann Pharmacother. 1992; 26:1300. [IDIS 302816] [PubMed 1421659]
16. Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother. 1994; 28:405-6. Letter.
17. Dista. Prozac (fluoxetine hydrochloride) prescribing information. In: Physicians’ desk reference. 48th ed. Montvale, NJ: Medical Economics Company; 1994:877-80.
18. Montastruc JL, Chamontin B, Senard JM et al. Pseudophaeochromocytoma in parkinsonian patient treated with fluoxetine plus selegiline. Lancet. 1993; 341:555. [IDIS 311064] [PubMed 8094789]
19. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991; 337:246. [IDIS 276804] [PubMed 1670882]
20. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991; 337:246. [IDIS 276804] [PubMed 1670882]
21. Asch DA, Parker RM. The Libby Zion case: one step forward or two steps backward? N Engl J Med. 1988; 318:771-5. Letter.
22. Youdim MBH. Pharmacology of MAO B inhibitors: mode of action of (—)deprenyl in Parkinson’s disease. J Neural Transm. 1986; 22(Suppl):91-105.
23. Knoll J. The pharmacology of (—)deprenyl. J Neural Transm. 1986; 22(Suppl):75-89.
24. Riederer P, Youdim MBH. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem. 1986; 46:1359-65. [PubMed 2420928]
25. Kalir A, Sabbagh A, Youdim MBH. Selective acetylenic ’suicide’ and reversible inhibitors of monoamine oxidase types A and B. Br J Pharmacol. 1981; 73:55-64. [PubMed 7284698]
26. Reynolds GP, Elsworth JD, Blau K et al. Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol. 1978; 6:542-4. [IDIS 108923] [PubMed 728327]
27. Fowler JS, Volkow ND, Logan J et al. Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson’s disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327. Neurology. 1993; 43:1984-92. [IDIS 321175] [PubMed 8413955]
28. Fowler JS, MacGregor RR, Wolf AP et al. Mapping human brain monoamine oxidase A and B with11C-labeled suicide inactivators and PET. Science. 1987; 235:481-5. [IDIS 225436] [PubMed 3099392]
29. Meeker JE, Reynolds PC. Postmortem tissue methamphetamine concentrations following selegiline administration. J Analytic Toxicol. 1990; 14:330-1.
30. Reynolds GP, Riederer P, Sandler M et al. Amphetamine and 2-phenylethylamine in post-mortem parkinsonian brain after (—)deprenyl administration. J Neural Transm. 1978; 43:271-7. [PubMed 745019]
31. Elsworth JD, Sandler M, Lees AJ et al. The contribution of amphetamine metabolites of (—)-deprenyl to its antiparkinsonian properties. J Neural Transm. 1982; 54:105-10. [PubMed 6809891]
32. Heinonen EH, Myllylä V, Sotaniemi K et al. Pharmacokinetics and metabolism of selegiline. Acta Neurol Scand. 1989; 126:93-9.
33. Arnett CD, Fowler JS, MacGregor RR et al. Turnover of brain monoamine oxidase measured in vivo by positron emission tomography usingl-[11C]deprenyl. J Neurochem. 1987; 49:522-7. [PubMed 3110375]
34. Baronti F, Davis TL, Boldry RC et al. Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging. Neurology. 1992; 42:541-4. [IDIS 293667] [PubMed 1549214]
35. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food Drug and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 30, 1994. Rockville, MD; 1994 Jul.
36. Lieberman A. Long-term experience with selegiline and levodopa in Parkinson’s disease. Neurology. 1992; 42(Suppl 4):32-6. [IDIS 295410] [PubMed 1584430]
37. Paulson GW. Management of the patient with newly-diagnosed Parkinson’s disease. Geriatrics. 1993; 48:30-40. [IDIS 309606] [PubMed 8094362]
38. Csanda E, Tárczy M. Selegiline in the early and late phases of Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):105-13.
39. Birkmayer W, Birkmayer GD. Effect of (—)deprenyl in long-term treatment of Parkinson’s disease. J Neural Transm. 1986; 22(Suppl):219-25.
40. Lieberman AN, Gopinathan G, Neophytides A et al. Deprenyl versus placebo in Parkinson disease: a double-blind study. N Y State J Med. 1987; 87:646-9. [IDIS 236827] [PubMed 3124027]
41. Gaál J, Hermecz I. Medicinal chemistry of present and future MAO-B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:75-108.
42. Polymeropoulos EE. l-deprenyl: a unique MAO-B inhibitor. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:109-124.
43. Magyar K. Pharmacology of monoamine oxidase type B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:125-43.
44. Heinonen EH, Anttila MI, Lammintausta RAS. Pharmacokinetics and clinical pharmacology of selegiline. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:201-13.
45. Paul W, Szelenyi I. Chemical structures and pharmacological features of MAO-B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:339-58.
46. Nickel B, Borbe HO, Szelenyi I. Effect of selegiline and desmethyl-selegiline on cortical electric activity in rats. J Neural Transm. 1990; 32(Suppl):139-44.
47. Borbe HO, Niebch G, Nickel B. Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethyl-selegiline in the rat. J Neural Transm. 1990; 32(Suppl):131-7.
48. Somerset Pharmaceuticals. Eldepryl (selegiline hydrochloride) protocol for Parkinson’s disease. Tampa, FL.
49. Poewe W, Gerstenbrand F, Ransmayr G. Experience with selegiline in the treatment of Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):131-5.
50. Golbe LI, Duvoisin RC. Double-blind trial of R-(—)-deprenyl for the “on-off” effect complicating Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):123-9.
51. Elizan TS. (—)-deprenyl combined withl-dopa in the treatment of Parkinson’s disease. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:277-88.
52. Fischer PA, Baas H. Therapeutic efficacy of R-(—)-deprenyl as adjuvant therapy in advanced parkinsonism. J Neural Transm. 1987; 25(Suppl):137-47.
53. The Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1989; 321:1364-71. [IDIS 260856] [PubMed 2509910]
54. The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1993; 328:176-83. [IDIS 308618] [PubMed 8417384]
55. Tetrud JW, Langston JW. The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science. 1989; 245:519-22. [IDIS 257789] [PubMed 2502843]
56. Scherokman B. Tocopherol and deprenyl for patients with early Parkinson disease. ACP J Club. 1993; May/June:71.
57. Calne DB. Treatment of Parkinson’s disease. N Engl J Med. 1993; 329:1021-7. [IDIS 320203] [PubMed 8366903]
58. Olanow CW, Calne D. Does selegiline monotherapy in Parkinson’s disease act by symptomatic or protective mechanisms? Neurology. 1991; 42(Suppl 4):13-26. (IDIS 295409)
59. Olanow CW. The early treatment of Parkinson’s disease. Neurology. 1993; 43:S30-1. [IDIS 310551] [PubMed 8414016]
60. Ward CD. Does selegiline delay progression of Parkinson’s disease? A critical re-evaluation of the DATATOP study. J Neurol Neurosurg Psychiatr. 1994; 57:217-20. [PubMed 8126510]
61. Burke WJ, Ranno AE, Roccaforte WH et al. L-deprenyl in the treatment of mild dementia of the alzheimer type: preliminary results. J Am Geriatr Soc. 1993; 41:367-70. [IDIS 312561] [PubMed 8463521]
62. Burke WJ, Roccaforte WH, Wengel SP et al. L-deprenyl in the treatment of mild dementia of the alzheimer type: results of a 15-month trial. J Am Geriatr Soc. 1993; 41:1219-25. [IDIS 321777] [PubMed 8227897]
63. Schneider LS, Olin JT, Pawluczyk S. A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in alzheimer’s disease. Am J Psychiatr. 1993; 150:321-3. [IDIS 309451] [PubMed 8422085]
64. Golbe LI. Long-term efficacy and safety of deprenyl (selegiline) in advanced Parkinson’s disease. Neurology. 1989; 39:1109-11. [IDIS 258495] [PubMed 2503769]
65. Coleman RJ. Current drug therapy for Parkinson’s disease: a review. Drug Aging. 1992; 2:112-24.
66. Lieberman AN, Gopinathan G, Neophytides A et al. Deprenyl in the treatment of Parkinson’s disease: a specific type B monoamine oxidase inhibitor. N Y State J Med. 1984; 84:13-6. [IDIS 180794] [PubMed 6422358]
67. Saint-Cyr JA, Taylor AE, Long AE. Neuropsychological and psychiatric side effects in the treatment of Parkinson’s disease. Neurology. 1993; 43(Suppl 6):S47-52.
68. Waters CH. Side effects of selegiline (Eldepryl). J Geriatr Psychiatr Neurol. 1992; 5:31-4.
69. Rowland MJ, Bransome ED Jr, Hendry LB. Hypoglycemia caused by selegiline, an antiparkinsonian drug: can such side effects be predicted? J Clin Pharmacol. 1994; 34:80-5. (IDIS 325202)
70. Somerset Pharmaceuticals. Eldepryl (selegiline hydrochloride) product monograph. Tampa, FL; 1990 Oct.
71. Subramanya KS, Motimaya AM, Curry PT et al. Assessment of genotoxicity of two anti-parkinsonian drugs (selegiline hydrochloride and bromocryptine mesylate) in vivo in mouse bone marrow cells. Toxicol Lett. 1993; 66:221-30. [PubMed 8475502]
72. Magyar K, Tóthfalusi L. Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm. 1984; 36:373-84. [PubMed 6441926]
73. The Parkinson Study Group. DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol. 1989; 46:1052-60. [PubMed 2508608]
74. Gewirtz GR, Sharif Z, Cadet JL et al. Selegiline for neuroleptic-induced parksinsonism. Pharmacopsychiatry. 1993; 26:128-9. [PubMed 7901857]
75. Menza MA, Golbe LI. Hypomania in a patient receiving deprenyl (selegiline) after adrenal-striatal implantation for Parkinson’s disease. Clin Neuropharmcol. 1988; 11:549-51.
76. Frankel JP, Kempster PA, Stibe CMH et al. A double-blind, controlled study of high-dose L-deprenyl in the treatment of Parkinson’s disease. Clin Neuropharmacol. 1989; 12: 448-51.
77. Mally J, Kovacs AB, Stone TW. Delayed development of symptomatic improvement by (—)-deprenyl in Parkinson’s disease. J Neurol Sci. 1995; 134:143-5. [PubMed 8747857]
78. Koutsilieri E, O’Callaghan JFX, Chen T et al. Selegiline enhances survival and neurite outgrowth of MPP+-treated dopaminergic neurons. Eur J Pharmacol. 1994; 269:R3-4. [PubMed 7895766]
79. Carrillo MC, Ivy GO, Milgram NW et al. (—)Deprenyl increases activities of superoxide dismutase (SOD) in striatum of dog brain. Life Sci. 1994; 54:1483-9. [PubMed 8190023]
80. Gerlach M, Youdim MBH, Riederer P. Is selegiline neuroprotective in Parkinson’s disease? Gen Pharmacol. 1994; 41:177-88.
81. Iwasaki Y, Ikeda K, Shiojima T et al. Deprenyl enhances neurite outgrowth in cultured rat spinal ventral horn neurons. J Neurol Sci. 1994; 125:11-3. [PubMed 7964880]
82. Knoll J, Miklya I. Multiple, small dose administration of (-)deprenyl enhances catecholaminergic activity and diminishes serotoninergic activity in the brain and these effects are unrelated to MAO-B inhibition. Arch Int Pharmacodyn Ther. 1994; 328:1-15. [PubMed 7893186]
83. Di Paola R, Uitti RJ. Early detection of Parkinson’s disease: implications for treatment. Drugs Aging. 1996; 9:159-68. [PubMed 8877310]
84. Montastruc JL, Rascol O, Senard JM. New directions in the drug treatment of Parkinson’s disease. Drugs Aging. 1996; 9:169-84. [PubMed 8877311]
85. Fahn S. Controversies in the therapy of Parkinson’s disease. Adv Neurol. 1996; 69:477-86. [PubMed 8615168]
86. Fowler JS, Fazzini E,Volkow ND. Deprenyl and levodopa and Parkinson’s disease progression. Ann Neurol. 1996; 40:267-8. [IDIS 371739] [PubMed 8773616]
87. Mahmood I, Marinac JS, Willsie S et al. Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers. Biopharm Drug Dispos. 1995; 16:535-45. [IDIS 354374] [PubMed 8785378]
88. Kikura R, Nakahara Y. Hair analysis for drugs of abuse. IX. Comparison of deprenyl use and methamphetamine use by hair analysis. Biol Pharm Bull. 1995; 18:267-72. [PubMed 7742796]
89. Lees AJ on behalf of the Parkinson’s Disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease. BMJ. 1995; 311:1602-7. [IDIS 357845] [PubMed 8555803]
90. Bergus G. Treatment of Parkinson’s disease. J Fam Pract. 1996; 42:457-8. [PubMed 8642360]
91. Calne DB. Selegiline in Parkinson’s disease: no neuroprotective effect: increased mortality. BMJ. 1995; 311:1583-4. [IDIS 357844] [PubMed 8555790]
92. Golbe LI, Lieberman AN, Muenter MD et al. Deprenyl in the treatment of symptom fluctuations in advanced Parkinson’s disease. Clin Neuropharmacol. 1988; 11:45-55. [PubMed 3127050]
93. Ahlskog JE. Treatment of early Parkinson’s disease: are complicated strategies justified? Mayo Clin Proc. 1996; 71:659-70.
94. Parkinson’s Disease Research Group in the United Kingdom. Comparisons of therapeutic effects of levodopa, levodopa and selegiline, and bromocriptine in patients with early, mild Parkinson’s disease: three year interim report. BMJ. 1993; 307:469-72. [PubMed 8400928]
95. Anon. Selegiline in Parkinsonism: a need for radical reappraisal. WHO Drug Info. 1996; 10:21-4.
96. Hughes AJ. Drug treatment of Parkinson’s disease in the 1990s: achievements and future possibilities. Drugs. 1997; 53:195-205. [PubMed 9028741]
97. Garcia-Monco JC, Padierna A, Gomez Beldarrain M. Selegiline, fluoxetine, and depression in Parkinson’s disease. Mov Disord. 1995; 10:352. [PubMed 7651457]
98. Waters CH. Fluoxetine and selegiline—lack of significant interaction. Can J Neurol Sci. 1994; 21:259-61. [PubMed 8000982]
99. Solvay Pharmaceuticals. Luvox (fluvoxamine maleate) tablets prescribing information (dated 1996 Aug). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2723-7.
100. SmithKline Beecham Pharmaceuticals. Paxil (paroxetine hydrochloride) tablets prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2681-6.
101. Pfizer, Inc. Zoloft (sertraline hydrochloride) tablets prescribing information (dated 1996 Apr). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2051-3.
102. Zeneca Pharmaceuticals. Elavil (amitriptyline hydrochloride) tablets and injection prescribing information (dated 1996 May). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2945-7.
103. Hoechst Marion Roussel, Inc. Norpramin (desipramine hydrochloride) tablets, USP, prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:1273-5.
104. Sano M, Ernesto C, Thomas RG et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997; 336:1216-22. [IDIS 383380] [PubMed 9110909]
105. Drachman DA, Leber P. treatment of Alzheimer’s disease—searching or a breakthrough, settling for less. N Engl J Med. 1997; 336:1245-7. [IDIS 383383] [PubMed 9110915]
106. Small GW, Rabins PV, Barry PP et al. Diagnosis and treatment of Alzheimer disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s associatioon, and the American geriatric Society. JAMA. 1997; 278:1363-71. [IDIS 393115] [PubMed 9343469]
107. American Psychiatric Association. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. Am J Psychiatry. 1997; 154(Suppl):1-39.
108. Mahmood I. Clinical pharmacokinetics and pharmacodynamics of selegiline: an update. Clin Pharmacokinet. 1997; 33:91-102. [PubMed 9260033]
109. Rohatagi S, Barrett JS, McDonald LJ et al. Selegiline percutaneous absorption in various species and metabolism by human skin. Pharmaceut Res. 1997; 14:50-5.
110. Heinonen EH, Anttila MI, Karnani HL et al. Desmethylselegiline, a metabolite od selegiline, is an irreversible inhibitor of monoamine oxidase type B in humans. J Clin Pharmacol. 1997; 37:602-9. [IDIS 390771] [PubMed 9243353]
111. Rohatagi S, Barrett JS, DeWitt KE et al. Integrated pharmacokinetic and metabolic modelng of selegiline and metabolites after transdermal administration. Biopharm Drug Dispos. 1997; 18:567-84. [IDIS 395160] [PubMed 9330778]
112. Pfeiffer RF. Antiparkinsonia agents: drug interactions of clinical significance. Drug Saf. 1996; 14:343-54. [PubMed 8800629]
113. Korn A, Wagner B, Moritz E et al. Tyramine pressor sensitivity in healthy subnjects during combined treatment with moclobemide and selegiline. Eur J Clin Pharmacol. 1996; 49:273-8. [IDIS 360563] [PubMed 8857072]
114. Haberny KA, Walsh SL, Ginn DH et al. Absence of acute cocaine interactions with the MAO-B inhibitor selegiline. Drug Alcohol Depend. 1995; 39:55-62. [PubMed 7587975]
115. Hauser RA, Zesiewicz TA. Sertraline for the treatment of depression in Parkinson’s disease. Mov Disord. 1997; 12:756-9. [PubMed 9380061]
116. Steur EN, Ballering LA. Moclobemide and selegiline in the treatment of depression in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997; 63:547. [PubMed 9343144]
117. American Psychiatric Association. American Psychiatric Association practice guidelines. Washington, DC: American Psychiatric Association. 1996:98,116.
118. Meperidine (Demerol) interactions: selegiline (Eldepryl). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:379.
119. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol. 1996; 39:29-36. [IDIS 362918] [PubMed 8572663]
120. Mäki-Ikola O, Heinonen E. Study design problems of DATATOP study analysis. Ann Neurol. 1996; 40:946-7. [IDIS 378319] [PubMed 9007106]
121. Penney JB, Shoulson I, Kieburtz K et al for the DATATOP Steering Committee and Investigators. Study design problems of DATATOP study analysis. Ann Neurol. 1996; 40:947-8.
122. Reviewers’ comments (personal observations).
123. Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1995:431-59.
124. Parkinson Study Group. Clinical outcome following placebo-controlled withdrawal of deprenyl (selegiline) among levodopa-treated DATATOP subjects. Movement Disord. 1997; 12:838.
125. Parkinson Study Group. Mortality in DATATOP: a multicenter trial in early Parkinson’s disease. Ann Neurol. (in press)
126. Richard IH, Kurlan R, Tanner C et al et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Neurology. 1997; 48:1070-7. [IDIS 385237] [PubMed 9109902]
127. Adelman A. Selegiline and vitamin E in Alzheimer’s disease. J Fam Pract. 1997; 45:98-100. [PubMed 9267360]
128. Pincus MM. Alpha-tocopherol and Alzheimer’s disease. N Engl J Med. 1997; 337:572. [IDIS 390514] [PubMed 9265106]
129. Doody RS, Stevens JC, Beck C et al. Practice parameter: management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2001; 56:1154-66. [IDIS 463599] [PubMed 11342679]
130. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.
131. Teva Neuroscience, Inc. Azilect (rasagiline mesylate) tablets prescribing information. Kansas City, MO; 2010 Mar. From DailyMed website.
132. Somerset Pharmaceuticals, Inc. Eldepryl (selegiline hydrochloride) capsules prescribing information. Tampa, FL; 1998 Jul.
133. Eli Lilly and Company. Cymbalta (duloxetine hydrochloride) delayed-release capsules prescribing information. Indianapolis, IN; 2011 Sep.