Professional Information

Selegiline (Systemic)

VA CLASSIFICATION
Primary: CN500

Commonly used brand name(s): Apo-Selegiline; Carbex; Eldepryl; Gen-Selegiline; Novo-Selegiline; Nu-Selegiline; SD Deprenyl; Selegiline-5.

Other commonly used names are
deprenil and deprenyl .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Category:

Antidyskinetic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Parkinsonism (treatment adjunct)—Selegiline is indicated for use with levodopa or levodopa and carbidopa combination in the treatment of idiopathic Parkinson's disease (paralysis agitans) ^{01} ^{03} ^{09} ^{13} ^{15} ^{16} ^{17} ^{18} ^{19} ^{24} ^{25} ^{27}.
—[Some studies have suggested that the initial use of selegiline may delay the need for addition of levodopa to the treatment regimen ^{13} ^{19} ^{21} ; in addition, these studies have shown that selegiline alone ^{21} or in combination with levodopa ^{03} ^{06} ^{07} ^{13} ^{15} may slow the progression of Parkinson's disease, possibly by preventing selective ^{17} destruction of dopaminergic ^{15} neurons in the substantia nigra ^{15} ^{17} . One retrospective study showed selegiline to possibly prolong the life span of patients with idiopathic Parkinson's disease ^{07} .]
—[The addition of selegiline to levodopa in patients experiencing fluctuating responses ^{09} ^{13} ^{15} ^{17} ^{18} ^{19} ^{27} (“wearing off” effect ^{13} ^{15} ^{17} ^{19} ^{24} ^{27} or “on-off” phenomenon ^{13} ^{14} ^{15} ^{18} ) may be of moderate benefit ^{09} ^{16} ^{24} ^{25} ^{27} . However, the initial response to selegiline may not be sustained ^{16} , with the degree of improvement declining ^{03} ^{18} over 6 months to 4 years ^{13} ^{15} ^{24} ^{27} . Selegiline is ineffective in advanced disease ^{03} ^{05} ^{19} with extreme fluctuations ^{16} . Motor control fluctuations may be due to factors other than the central pharmacokinetics of dopamine; hence prolongation of dopamine effects may fail in some cases to improve this problem ^{31} .]

Note: Preliminary studies have demonstrated that selegiline may be useful as an antidepressant ^{03} ^{05} ^{26} ^{28} ^{29}, usually when given in doses greater than those used for its antidyskinetic effect ^{26}. However, there are insufficient data to definitively establish effectiveness of selegiline and criteria for its use in mental depression ^{31} ^{40}.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    223.75 ^{01}

Mechanism of action/Effect:

The action of selegiline is thought to be related to its irreversible ^{01} ^{24} inhibition of monoamine oxidase type B (MAO B) ^{01} ^{09} ^{10} ^{11} ^{12} ^{13} ^{14} ^{15} ^{16} ^{17} ^{18} ^{20} ^{22} ^{23} ^{24} ^{25} ^{26} ^{27}, the major form of the enzyme in the human brain ^{01} ^{23} ^{24}. MAO B, which is involved in the oxidative deamination ^{03} ^{15} ^{25} of dopamine in the brain ^{03} ^{10} ^{24} ^{27}, is inhibited when selegiline binds covalently ^{12} ^{24} and stoichiometrically ^{12} to the isoalloxazine ^{12} flavin adenine dinucleotide (FAD) ^{01} ^{12} ^{24} at its active center ^{12}. Administration of 10 mg of selegiline a day ^{13} ^{15} ^{21} produces almost complete inhibition of MAO B ^{13} ^{15} ^{20} ^{21} ^{24} in the brain ^{15} ^{21} ^{24}. Selegiline becomes a nonselective inhibitor of all monoamine oxidase (MAO) at higher doses ^{01} ^{15} ^{23} ^{25}, possibly at 20 to 40 mg a day ^{01} ^{15} ^{25} ^{31}. At these doses, tyramine-mediated hypertensive reactions from MAO A blockade (“cheese reactions”) may occur ^{01} ^{15}.

Selegiline (or its metabolites) ^{31} may also act through other mechanisms to increase dopaminergic activity ^{01} ^{09} ^{19}, including interfering with dopamine re-uptake ^{01} ^{09} ^{15} ^{20} at the synapse ^{01}.

Absorption:

Rapidly absorbed from the gastrointestinal tract ^{03} ^{24} ^{27}.

Distribution:

Crosses the blood-brain barrier ^{03} ^{27}.

Biotransformation:

Rapidly ^{20} and completely ^{03} ^{04} metabolized to N-desmethyldeprenyl ^{01} ^{24}, l-methamphetamine, and l-amphetamine ^{01} ^{03} ^{09} ^{12} ^{14} ^{16} ^{20} ^{24} ^{25} ^{27} ^{31}.

Half-life:

The mean half-lives of the 3 active metabolites that were found in serum and urine following a single dose of selegiline are as follows ^{01}:

N-desmethyldeprenyl: 2 hours.

l-amphetamine: 17.7 hours.

l-methamphetamine: 20.5 hours.

Elimination:

Selegiline: 39 (range, 16 to 69) hours ^{24}.

Time to peak plasma concentration

0.5 to 2 hours ^{24}.

Duration of action:

Duration of clinical action depends on the regeneration time of MAO B ^{01} ^{24}.

Elimination:
    Renal ^{01} ^{03} ^{04} ^{20}; slow ^{20}. 45% of a 10 mg dose appears in the urine as metabolites ( N-desmethyldeprenyl, l-amphetamine, and l-methamphetamine) within 48 hours of ingestion ^{01}.

Precautions to Consider

Carcinogenicity

Long-term animal studies have revealed no evidence of carcinogenic effects ^{39}.

Pregnancy/Reproduction

Pregnancy—
Studies in humans have not been done ^{01}.

Studies in animals have not shown that selegiline causes adverse effects on the fetus ^{01}. Reproduction studies in rats and rabbits given approximately 250 and 350 times the comparable human dose, respectively, have revealed no evidence of teratogenic effects ^{39}.

FDA Pregnancy Category C ^{01}.

Breast-feeding

It is not known whether selegiline is excreted in breast milk ^{01}.

Pediatrics

No published pediatrics-specific information is available. Safety and efficacy have not been established ^{01}.

Geriatrics

No geriatrics-related problems have been documented in studies done to date that included elderly patients ^{31}.

Dental

Selegiline may decrease or inhibit salivary flow ^{01} ^{09} ^{14}, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

For all doses of selegiline
» Antidepressants, tricyclic^{42}^{46}^{51}    (asystole, diaphoresis, hypertension, syncope, changes in behavior and mental status, impaired consciousness, hyperpyrexia, seizures, muscular rigidity, and tremors have occurred with concurrent use of selegiline and tricyclic antidepressants. Concurrent use is not recommended; at least 14 days should elapse between discontinuation of selegiline and initiation of a tricyclic antidepressant ^{42} ^{51})

» Fluoxetine^{36}^{37}^{42}^{43}^{44}^{46}^{50}^{51} or
» Fluvoxamine^{46}^{50}^{51} or
» Nefazodone^{48}^{49}^{50}^{51} or
» Paroxetine^{42}^{46}^{50}^{51} or
» Sertraline^{42}^{45}^{46}^{50}^{51} or
» Venlafaxine^{47}^{48}^{49}^{50}^{51}    (a reaction resembling the serotonin syndrome has been reported rarely following concurrent use of selegiline with selective serotonin re-uptake inhibitors (SSRIs) ^{37} ^{42} ^{44} ^{45} ^{46} ^{51}. [The serotonin syndrome may occur as the result of combining a serotonergic agent with an MAO inhibitor. The syndrome may be manifest by mental status changes (confusion, hypomania), restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, and/or fever. If recognized early, the syndrome usually resolves quickly upon withdrawal of the offending agents.] ^{38} Concurrent use of selegiline with SSRIs ^{42} ^{45} ^{46} ^{50} ^{51} is not recommended because of the potential for autonomic instability, muscular rigidity, severe agitation, or delirium ^{46}. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of an SSRI ^{45} ^{46} ^{47}. However, because of the long half-lives of fluoxetine and its active metabolite, at least 5 weeks [approximately 5 half-lives] should elapse between discontinuation of fluoxetine and initiation of therapy with an MAO inhibitor ^{36} ^{43} ^{46}. Also, based on the half-life of venlafaxine, at least 7 days should elapse between discontinuation of venlafaxine and initiation of therapy with an MAO inhibitor ^{47}.)

Levodopa^{15}^{18}^{24}^{25}^{27}^{31}^{33}    (although selegiline is used in conjunction with levodopa, it may enhance levodopa-induced dyskinesias, nausea, orthostatic hypotension, confusion, and hallucinations; reduction of levodopa dosage may be necessary within 2 to 3 days after the initiation of selegiline therapy)

» Meperidine^{01}^{35} , and possibly other opioid (narcotic) analgesics^{01}    (at least one interaction of meperidine with selegiline has been reported; concurrent use of meperidine with nonselective monoamine oxidase inhibitors [MAOIs] may produce immediate excitation, sweating, rigidity, and severe hypertension; in some patients, hypotension, severe respiratory depression, coma, convulsions, hyperpyrexia, vascular collapse, and death may occur; avoidance of meperidine use within 2 to 3 weeks following MAO inhibition is recommended; other opioid analgesics such as morphine are not likely to cause such severe reactions and may be used cautiously in reduced dosage in patients receiving MAOIs; however, it is recommended that a small test dose [one quarter of the usual dose] or several small incremental test doses over a period of several hours should first be administered to permit observation of any adverse effects; caution is also recommended in the use of alfentanil, fentanyl, or sufentanil as an adjunct to anesthesia if the patient has received an MAOI within 14 days; because the risk of a significant interaction has been questioned, the use of a small test dose is advised to detect any possible interaction ^{30})

For doses of 20 mg or more of selegiline per day
» Tyramine- or other high pressor amine–containing foods and beverages, such as aged cheese; fava or broad bean pods; yeast/protein extracts; smoked or pickled meats, poultry, or fish; fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; sauerkraut; any overripe fruit; beer; reduced-alcohol and alcohol-free beer and wine; red and white wines; sherry; and liqueurs    (concurrent use with MAOIs, including selegiline in doses of 20 mg a day or greater ^{31} ^{32}, may cause sudden and severe hypertensive reactions; reactions are usually limited to a few hours and are easily treated with rapidly acting hypotensive agents [such as labetalol, nifedipine, or, if necessary in severe cases refractory to other agents, phentolamine]; severity of reaction depends on amount of tyramine ingested, rate of gastric emptying, and length of interval between dose of MAOI and ingestion of tyramine; when MAOIs are discontinued, dietary restrictions must continue for at least 2 weeks; other tyramine- or high pressor amine–containing foods, such as yogurt, sour cream, cream cheese, cottage cheese, chocolate, and soy sauce, if eaten when fresh and in moderation, are considered unlikely to cause serious problems ^{30} ^{34})

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
Dementia, profound^{41} or
Psychosis, severe^{41} or
Tardive dyskinesia^{41} or
Tremor, excessive^{41}    (condition may be exacerbated)

» Peptic ulcer disease, history of^{13}^{15}^{24}^{27}    (activation of pre-existing ulcers may occur, probably due to stimulation of the H ₂ receptors in the stomach ^{15} or inhibition of MAO-mediated gastric histamine catabolism ^{24})

Sensitivity to selegiline^{01}

Side/Adverse Effects

Note: Selegiline enhances the dose-related side effects of levodopa ^{15}, but few side effects are attributable to selegiline itself ^{13} ^{18} ^{21} ^{24} ^{27}. When selegiline is used as an adjunct to levodopa or levodopa and carbidopa combination, adverse effects can usually be ameliorated ^{25} ^{27} by reducing the dose of levodopa or levodopa and carbidopa ^{15} ^{18} ^{24} ^{25} ^{27}.
In addition, selegiline may cause elevation of liver enzymes ^{13} ^{31}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent

Dyskinesias^{01}^{03}^{09}^{13}^{15}^{24} (increase in unusual movements of body)

mood or other mental changes^{01}^{09}

Incidence less frequent or rare

Angina pectoris, new or increased^{01} (chest pain)

arrhythmias^{01} (irregular heartbeat)

asthma^{01} (wheezing, difficulty in breathing, or tightness in chest)

bradycardia, sinus^{01} (slow heartbeat)

edema, peripheral^{01} (swelling of feet or lower legs)

motor/coordination/extrapyramidal effects^{01} (difficulty in speaking; loss of balance control; uncontrolled movements, especially of face, neck, and back; restlessness or desire to keep moving; twisting movements of body)

gastrointestinal bleeding^{15}^{27} (bloody or black, tarry stools; severe stomach pain; vomiting of blood or material that looks like coffee grounds)

hallucinations^{01}^{09}^{13}^{15}^{24}^{27}

headache, severe^{01}

hypertension, severe^{01}

orthostatic hypotension^{03}^{09}^{26} (dizziness or lightheadedness, especially when getting up from a lying or sitting position)

prostatic hypertrophy^{01} (difficult or frequent urination)

tardive dyskinesia^{01} (lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements; uncontrolled movements of arms and legs)

Symptoms of hypertensive crisis ^{30}

Chest pain, severe

enlarged pupils

fast or slow heartbeat

headache, severe

increased sensitivity of eyes to light

increased sweating, possibly with fever or cold, clammy skin

nausea or vomiting, severe

stiff or sore neck

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent

Abdominal or stomach pain^{01}

dizziness^{01}^{09}^{14}^{21}^{26}^{27} or feeling faint^{01}

dryness of mouth^{01}^{09}^{14}

insomnia^{01}^{13}^{14}^{21}^{24}^{26}^{27} (trouble in sleeping)

nausea^{01}^{03}^{09}^{21}^{26}^{27} or vomiting^{01}

Incidence less frequent or rare

Anxiety^{01} , nervousness^{01} , or restlessness^{01}

apraxia, increased^{01} (inability to move)

blepharospasm^{01} (sudden closing of eyelids)

blurred or double vision^{01}

body ache^{01} or back or leg pain^{01}

bradykinesia, increased^{01} (slowed movements)

chills^{01}

constipation^{01} or diarrhea^{01}

diaphoresis^{01} (increased sweating)

drowsiness^{01}

headache^{01}^{21}

heartburn^{01}

hypertension^{01}^{13} or hypotension^{01} (high or low blood pressure)

impaired memory^{01}^{33} —more frequent with doses greater than 10 mg a day

slow or difficult urination^{01}

frequent urge to urinate^{01}

irritability, temporary^{01}

loss of appetite^{01} or weight loss^{01}

muscle cramps^{01} or numbness of fingers or toes^{01}

palpitations^{01} or tachycardia^{01} (pounding or fast heartbeat)

paresthesias, circumoral^{01}^{09} (burning of lips or mouth), or burning of throat^{01}

photosensitivity^{01} (increased sensitivity of skin and eyes to sunlight)

skin rash^{01}

tinnitus^{01} (ringing or buzzing in ears)

taste changes^{01}^{09}

unusual feeling of well-being^{21}

unusual tiredness^{01}^{14} or weakness^{01}

With doses greater than 10 mg a day

Bruxism^{01} (clenching, gnashing, or grinding teeth)

muscle twitches^{01} or myoclonic jerks^{01}^{26} (sudden jerky movements of body)
Note: Bruxism and myoclonic jerks may be considered to be adverse effects only if not previously present and beginning shortly after the start of therapy with selegiline. ^{31}

Overdose
For specific information in the agents used in the management of selegiline overdose, see:
   • Charcoal, Activated (Oral-Local) monograph.
For more information on the management of overdose of unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
No specific information is available regarding overdoses with selegiline ^{01}. Since overdose is likely to cause significant inhibition of both MAO type A and type B, symptoms of overdose may resemble those of nonselective MAO inhibitors ^{01}.
Symptoms of MAOI overdose ^{01}

Agitation or irritability

chest pain

convulsions

cool, clammy skin

diaphoresis (increased sweating)

dizziness, severe, or fainting

fast or irregular pulse, continuing

high or low blood pressure

hyperpyrexia (high fever)

opisthotonus (severe spasm where the head and heels are bent backward and the body arched forward)

respiratory depression (troubled breathing)

trismus (difficulty opening the mouth; lockjaw)

Note: Symptoms resulting from overdose may be absent or minimal for nearly 12 hours after ingestion ^{01}, and develop slowly thereafter, reaching a maximum in 24 ^{01} to 48 hours ^{30}. Death has resulted. ^{30} Immediate hospitalization and close monitoring of patient is essential during this period ^{01} ^{30}.

Treatment of overdose
Treatment may include the following:

To decrease absorption:
Induction of emesis or gastric lavage with protected airway followed by instillation of charcoal slurry in early overdose ^{01}.

Specific treatment:
Treatment of signs and symptoms of central nervous system (CNS) stimulation with diazepam, administered intravenously and slowly ^{01}. Phenothiazine derivatives should be avoided ^{01}.

Treatment of hypotension and vascular collapse with intravenous fluids and, if necessary, a dilute pressor agent ^{01}. Adrenergic agents may produce a markedly increased pressor response ^{01}.

Vigorous treatment of hyperpyrexia ^{01} with antipyretics and a cooling blanket ^{30}.

Monitoring:
Close monitoring of body temperature ^{01}.

Supportive care:
Maintenance of fluid and electrolyte balance ^{01}.

Support of respiration by management of the airway, and mechanical ventilation with the use of supplemental oxygen, as required ^{01}.

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Selegiline (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to selegiline ^{01}
Other medications, especially fluoxetine, fluvoxamine, meperidine and possibly other narcotic (opioid) analgesics, nefazodone, paroxetine, sertraline, tricyclic antidepressants, or venlafaxine
Other medical problems, especially a history of peptic ulcer disease

Proper use of this medication
» Importance of not taking more medication than the amount prescribed ^{01}; to do so may increase the risk of side effects
Missed dose: Taking as soon as possible; not taking in the late afternoon or evening; not taking if almost time for next dose; not doubling doses.

» Proper storage

Precautions while using this medication
» If taking 20 mg or more of selegiline a day, avoiding tyramine-containing foods, alcoholic beverages, and large quantities of caffeine-containing beverages, over-the-counter cold and cough medicines, and other medications, unless prescribed

» Checking with hospital emergency room or physician if symptoms of hypertensive crisis develop

» Possibility of orthostatic hypotension; caution when getting up suddenly from a lying or sitting position

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dryness of mouth continues for more than 2 weeks

Side/adverse effects
Signs of potential side effects, especially dyskinesias, mood or mental changes, angina pectoris, arrhythmias, asthma, bradycardia, peripheral edema, extrapyramidal effects, hallucinations, severe headache, severe hypertension, gastrointestinal bleeding, orthostatic hypotension, prostatic hypertrophy, and tardive dyskinesia

General Dosing Information
Selegiline should not be used in the treatment of Parkinson's disease at doses exceeding 10 mg a day because of the risks associated with nonselective inhibition of monoamine oxidase (MAO) ^{01} ^{43} ^{46}. A tyramine-mediated hypertensive reaction has been reported when selegiline was administered at a dose of 20 mg a day ^{32}. In addition, selegiline in doses greater than 10 mg a day has not demonstrated increased effectiveness in the treatment of Parkinson's disease ^{01}.

When selegiline is used as an adjunct to levodopa or levodopa and carbidopa combination, adverse effects such as involuntary movements or hallucinations may result, and doses of levodopa may need to be reduced. If necessary, doses of levodopa should be reduced after 2 to 3 days by 10 to 30%, and possibly by as much as 50% with continued therapy ^{01} ^{03} ^{09} ^{10} ^{12} ^{13} ^{15} ^{18} ^{19} ^{24} ^{27}.

Because selegiline may produce insomnia ^{01} ^{21} ^{24} ^{26} ^{27}, it should not be administered in the late afternoon or evening ^{27}.

Diet/Nutrition
Selegiline should be administered with breakfast and lunch ^{01} ^{27} to minimize possible nausea and insomnia ^{27}.

When monoamine oxidase inhibitors, including selegiline at doses of 20 mg a day or greater ^{31} ^{32}, are used concurrently with foods and beverages containing tyramine or other high pressor amines, sudden and severe hypertensive reactions may result. These reactions are usually limited to a few hours and are easily treated with rapidly acting hypotensive agents (such as labetalol, nifedipine, or, if necessary in severe cases refractory to other agents, phentolamine). The severity of the reaction depends on the amount of tyramine ingested, the rate of gastric emptying, and the length of the interval between the dose of MAO inhibitor and ingestion of tyramine. When MAO inhibitors are discontinued, dietary restrictions must continue for at least 2 weeks ^{30}. Foods and beverages containing tyramine or other high pressor amines include aged cheese; fava or broad bean pods; yeast/protein extracts; smoked or pickled meats, poultry, or fish; fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; sauerkraut; any overripe fruit; beer; reduced-alcohol and alcohol-free beer and wine; red and white wines; sherry; and liqueurs. Other foods, such as yogurt, sour cream, cream cheese, cottage cheese, chocolate, and soy sauce, if eaten when fresh and in moderation, are considered unlikely to cause serious problems ^{30} ^{34}.

Oral Dosage Forms

SELEGILINE HYDROCHLORIDE CAPSULES

Usual adult dose
Parkinsonism
Oral, 5 mg two times a day, at breakfast and lunch.

Note: In some cases, some clinicians recommend that the total daily dose be divided (2.5 mg four times a day) to decrease the side effects induced by concomitant administration of levodopa ^{31}.

Usual pediatric dose
Safety and efficacy have not been established.

Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—

5 mg (Rx) [Eldepryl]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Avoid alcoholic beverages.

SELEGILINE HYDROCHLORIDE TABLETS USP

Usual adult dose
See Selegiline Hydrochloride Capsules .

Usual pediatric dose
See Selegiline Hydrochloride Capsules .

Usual geriatric dose
See Selegiline Hydrochloride Capsules .

Strength(s) usually available
U.S.—

5 mg (Rx) [Carbex][Generic]

Canada—

5 mg (Rx) [Apo-Selegiline] [Eldepryl] [Gen-Selegiline] [Novo-Selegiline] [Nu-Selegiline] [SD Deprenyl] [Selegiline-5]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Avoid alcoholic beverages.

Revised: 01/21/1998

References

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Martindale 1989: 1021-2.

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Goodman & Gilman, 7th ed.: 424; 483.

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Fischer PA, Baas H. Therapeutic efficacy of R-(—)-deprenyl as adjuvant therapy in advanced parkinsonism. J Neural Transm 1987; 25(Suppl): 137-47.

LeWitt PA. New perspectives in the treatment of Parkinson's disease. Clinical Neuropharmacology 1986; 9(Suppl 1): S37-S54.

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Karoum F, et al. Metabolism of (—) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment. Neurology 1982; 32: 503-9.

Tetrud JW, Langston JW. The effect of deprenyl (Selegiline) on the natural history of Parkinson's disease. Science 1989 Aug 4; 245(4917): 519-22.

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Golbe LI, et al. Deprenyl in the treatment of symptom fluctuations in advanced Parkinson's disease. Clin Neuropharmacol 1988 Feb; 11(1): 45-55.

Mann JJ, et al. 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.

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McGrath PJ, Stewart JW, Harrison W, Wager S, Nunes EN, Quitkin FM. A placebo-controlled trial of L-deprenyl in atypical depression. Psychopharmacol Bull 1989; 25(1): 63-7.

USP DI 1990: Antidepressants, Monoamine Oxidase (MAO) Inhibitor (Systemic) monograph.

Panelist comments, 1/90.

McGrath PJ, Stewart JW, Quitkin FM. A possible L-deprenyl induced hypertensive reaction. J Psychopharmacology 1989 Aug; 9: 310-1.

Panelist comment, 2/90.

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Eldepryl product monograph (Deprenyl Research Limited), Rev 4/14/92, Rec 6/9/92.

Dear Doctor letter. Somerset Pharmaceuticals, Inc. 11/14/94.

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Montastruc JL, Chamontin B, Senard JM, et al. Pseudophaeochromocytoma in parkinsonian patient treated with fluoxetine plus selegiline. Lancet 1993 Feb; 341: 555.

Reviewer comment, 10/25/92.

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Dear Doctor letter. Wyeth-Ayerst Laboratories. 12/28/94.

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