Here is info about selegiline (Deprenyl, Eldepryl) from the "PDR Family
Guide to Prescription Drugs" (the consumer's version of the PDR - the
Physician's Desk Reference).
It is followed by a large number of research abstracts that I found interesting.

There is quite a lot here about the risks of combining selegiline with
tricyclics or SSRI's.

By the way the recommended dosages listed near the bottom are for people
with parkinson's disease. For purposes of general neuroprotection/anti-aging,
the appropriate dose would be much smaller, in the range of 1 to 5 mg per day.

Pronounced: ELL-dep-rill
Generic name: Selegiline hydrochloride
Also known as Deprenyl


Why is this drug prescribed?

Eldepryl is prescribed along with Sinemet (levodopa/carbidopa) for people
with Parkinson's disease. It is used when Sinemet no longer seems to be
working well. Eldepryl has no effect when taken by itself; it works only in
combination with Larodopa (levodopa) or Sinemet.

Parkinson's disease, which causes muscle rigidity and difficulty with
walking and talking, involves the progressive degeneration of a particular
type of nerve cell. Early on, Larodopa or Sinemet alone may alleviate the
symptoms of the disease. In time, however, these medications work less well;
their effectiveness seems to switch on and off at random, and the individual
may begin to experience side effects such as involuntary movements and
"freezing" in mid-motion.

Eldepryl may be prescribed at this stage of the disease to help restore the
effectiveness of Larodopa or Sinemet. When you begin to take Eldepryl, you
may need a reduced dosage of the other medication.


Most important fact about this drug

Eldepryl belongs to a class of drugs known as MAO inhibitors. These drugs
can interact with certain foods--including aged cheeses and meats, pickled
herring, beer, and wine--to cause a life-threatening surge in blood
pressure. At the dose recommended for Eldepryl, this interaction is not a
problem. But for safety's sake, you may want to watch your diet; and you
should never take more Eldepryl than the doctor prescribed.


How should you take this medication?

Take Eldepryl and your other Parkinson's medication exactly as prescribed.

--If you miss a dose...

Take it as soon as you remember. If you do not remember until late afternoon
or evening, skip the dose you missed and go back to your regular schedule.
Never take 2 doses at once.

--Storage instructions...

Store at room temperature.


What side effects may occur?

Side effects cannot be anticipated. If any develop or change in intensity,
inform your doctor as soon as possible. Only your doctor can determine if it
is safe for you to continue taking Eldepryl.

Side effects may include:
Abdominal pain, abnormal movements, abnormally fast walking, aches,
agitation, angina (crushing chest pain), anxiety, apathy, asthma, back pain,
behavior or mood changes, bleeding from the rectum, blurred vision, burning
lips and mouth or throat, chills, confusion, constipation, delusions,
depression, diarrhea, difficulty swallowing, disorientation, dizziness,
double vision, drowsiness, dry mouth, excessive urination at night, eyelid
spasm, facial grimace, facial hair, fainting, falling down, freezing,
frequent urination, general feeling of illness, hair loss, hallucinations,
headache, heartburn, heart palpitations, heart rhythm abnormalities, "heavy
leg", high blood pressure, hollow feeling, inability to carry out purposeful
movements, inability to urinate, increased or excessive sweating, increased
tremor, insomnia, involuntary movements, irritability, lack of appetite, leg
pain, lethargy, light-headedness upon standing up, loss of balance, low
blood pressure, lower back pain, migraine, muscle cramps, nausea,
nervousness, numbness in toes/fingers, overstimulation, pain over the eyes,
personality change, poor appetite, rapid heartbeat, rash, restlessness
(desire to keep moving), ringing in the ears, sensitivity to light, sexual
problems, shortness of breath, sleep disturbance, slow heartbeat, slow
urination, slowed body movements, speech problems, stiff neck, stomach and
intestinal bleeding, swelling of the ankles or arms and legs, taste
disturbance, tension, tiredness, twitching, urinary problems, vertigo, vivid
dreams or nightmares, vomiting, weakness, weight loss


Why should this drug not be prescribed?

Do not take Eldepryl if you are sensitive to or have ever had an allergic
reaction to it. Do not take narcotic painkillers such as Demerol while you
are taking Eldepryl.


Special warnings about this medication

Never take Eldepryl at a higher dosage than prescribed; doing so could put
you at risk for a dangerous rise in blood pressure. If you develop a severe
headache or any other unusual symptoms, contact your doctor immediately.

You may suffer a severe reaction if you combine Eldepryl with tricyclic
antidepressants such as Elavil and Tofranil, or with antidepressants that
affect serotonin levels, such as Prozac and Paxil. Wait at least 14 days
after taking Eldepryl before beginning therapy with any of these drugs. If
you have been taking antidepressants such as Prozac and Paxil, you should
wait at least 5 weeks before taking Eldepryl. This much time is needed to
clear the antidepressant completely from your system.


Possible food and drug interactions when taking this medication

If Eldepryl is taken with certain other drugs, the effects of either could
be increased, decreased, or altered. It is especially important to check
with your doctor before combining Eldepryl with the following:

Antidepressant medications that raise serotonin levels, such as Paxil,
Prozac, and Zoloft
Antidepressant medications classified as tricyclics, such as Elavil and
Narcotic painkillers such as Demerol, Percocet, and Tylenol with Codeine

Eldepryl may worsen side effects caused by your usual dosage of levodopa.


Special information if you are pregnant or breastfeeding

The effects of Eldepryl during pregnancy have not been adequately studied.
If you are pregnant or plan to become pregnant, inform your doctor
immediately. Although Eldepryl is not known to cause specific birth defects,
it should not be taken during pregnancy unless it is clearly needed. It is
not known whether Eldepryl appears in breast milk. As a general rule, a
nursing mother should not take any drug unless it is clearly necessary.


Recommended dosage


The recommended dose of Eldepryl is 10 milligrams per day divided into 2
smaller doses of 5 milligrams each, taken at breakfast and lunch. There is
no evidence of additional benefit from higher doses, and they increase the
risk of side effects.


The use of Eldepryl in children has not been evaluated.


Although no specific information is available about Eldepryl overdosage, it
is assumed, because of chemical similarities, that the symptoms would
resemble those of overdose with an MAO inhibitor antidepressant.

Symptoms of MAO inhibitor overdose may include:
Agitation, chest pain, clammy skin, coma, convulsions, dizziness,
drowsiness, extremely high fever, faintness, fast and irregular pulse,
hallucinations, headache (severe), high blood pressure, hyperactivity,
inability to breathe, irritability, lockjaw, low blood pressure (severe),
shallow breathing, spasm of the entire body, sweating
It is important to note that after a large overdose, symptoms may not appear
for up to 12 hours and may not reach their full force for 24 hours or more.
An overdose can be fatal. If you suspect an Eldepryl overdose, seek medical
attention immediately. Hospitalization is recommended, with continuous
observation and monitoring for at least 2 days.

Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group.
Richard IH ; Kurlan R ; Tanner C ; Factor S ; Hubble J ; Suchowersky O ; Waters C
University of Rochester Medical Center, Department of Neurology, NY 14642-8673, USA.
Neurology, 48(4):1070-7 1997 Apr
The manufacturer of deprenyl (selegeline; Eldepryl) (Somerset Pharmaceuticals, Tampa, FL) recently advised physicians to avoid prescribing the drug in combination with an antidepressant because of potentially serious CNS toxicity that may represent the serotonin syndrome. Manifestations of the serotonin syndrome vary but may include changes in mental status and motor and autonomic function. To better estimate the frequency of the serotonin syndrome in patients with Parkinson's disease (PD) treated with deprenyl and an antidepressant, we surveyed all investigators in the Parkinson Study Group. Based on estimates provided by the 47 investigators (75%) who responded, 4,568 patients were treated with the combination of deprenyl and an antidepressant medication. Eleven patients (0.24%) were reported to have experienced symptoms possibly consistent with the serotonin syndrome. Only two patients (0.04%) experienced symptoms considered to be serious. No deaths were reported. We also reviewed all published case reports and adverse experiences reported to the U.S. Food and Drug Administration and the manufacturer of Eldepryl. Available information indicates that serious adverse experiences resulting from the combined use of deprenyl and an antidepressant medication in patients with PD are quite rare and that the frequency of the true "serotonin syndrome" is even rarer.
Unique Identifier


Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine.
Galzin AM ; Langer SZ
Naunyn Schmiedebergs Arch Pharmacol, 333(3):330-3 1986 Jul
The 5-hydroxytryptamine (5HT) receptor agonist, 5-methoxytryptamine, inhibited in a concentration-dependent manner the electrically-evoked release of 3H-5HT from superfused rat hypothalamic slices, with an IC50 of 560 nmol/l, without affecting the spontaneous outflow of radioactivity. In the presence of the selective monoamine oxidase B (MAO B) inhibitor, (-)-deprenyl (1 mumol/l), the concentration-effect curve for 5-methoxytryptamine was shifted significantly to the left, and the IC50 was decreased to 25 nmol/l. Under the same experimental conditions, the potency of the 5HT receptor agonist lysergic acid diethylamide (LSD) at inhibiting the electrically-evoked release of 3H-5HT was the same in the presence as well as in the absence of (-)-deprenyl. The IC50 values for LSD were 34 nmol/l in the absence of deprenyl, and 31 nmol/l in the presence of the MAO B inhibitor. It is concluded that deprenyl potentiates the inhibition by 5-methoxytryptamine of 3H-5HT release, by preventing its inactivation through MAO B. Since 5-methoxytryptamine may be present in the pineal gland of some species, the potent effects of this 5-HT receptor agonist on serotoninergic neurotransmission may be of physiological relevance.
Unique Identifier

Lack of adverse interactions between concomitantly administered selegiline and citalopram.
Laine K ; Anttila M ; Heinonen E ; Helminen A ; Huupponen R ; M¨aki-Ikola O ; Reinikainen K ; Scheinin M
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Clin Neuropharmacol, 20(5):419-33 1997 Oct
We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg once daily for 4 days. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of both study drugs and their metabolites and plasma prolactin, adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 days to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiated by concomitantly administered selegiline. The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups indicated no signs of subclinical pharmacodynamic interaction between selegiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadministered compared with selegiline alone. However, no indication of a pharmacokinetic interaction was found in the analysis of serum concentrations of the three main metabolites of selegiline. The pharmacokinetics of citalopram remained unaffected by concomitant selegiline. The present results indicate lack of clinically relevant pharmacodynamic or pharmacokinetic interactions between selegiline and citalopram.
Unique Identifier
TI- Pharmacokinetics and metabolism of selegiline.
AU- Heinonen EH; Myllyl¨a V; Sotaniemi K; Lamintausta R; Salonen JS; Anttila
    M; Savij¨arvi M; Kotila M; Rinne UK
AD- Farmos Group Ltd, Research Center, Turku, Finland.
SR- Acta
    Neurol Scand Suppl, 126(-HD-):93-9  1989
AB- Selegiline is readily absorbed from the gastrointestinal tract. It is
    distributed rapidly into the tissues, including the brain. It is the
    L-form of selegiline that is an active MAO-B inhibitor, the D-(+)-form
    being 25 times less active. Selegiline is metabolised into
    L-(-)-desmethylselegiline (DES), L-(-)-amphetamine (A) and
    L-(-)-methamphetamine (MA), mainly in the liver. We measured the steady
    state concentrations of the metabolites in the serum and cerebrospinal
    fluid (CSF) of patients with Parkinson's or Alzheimer's diseases who were
    on continuous selegiline therapy. The mean concentrations in serum and
    CSF were similar, and were not affected by the addition of levodopa. The
    mean concentrations of patients with Alzheimer's or Parkinson's disease
    were 6.5 +/- 2.5 ng/ml for A, 14.7 +/- 6.5 ng/ml for MA and 0.9 +/- 0.7
    ng/ml for DES. The metabolites of selegiline were excreted in urine, and
    the recovery as metabolites was 87%. Due to the stereospecificity and the
    low CSF concentrations of the (-)amphetamine metabolites during the
    therapy with 10 mg selegiline, these metabolites do not seem to
    contribute significantly to the clinical efficacy of selegiline.
LA- Eng
UI- 90143749
MM- Parkinson Disease ME; Phenethylamines ME; Phenethylamines PK; Selegiline
    ME; Selegiline PK
NN- Aged; Alzheimer Disease DT; Alzheimer Disease ME; Female; Human; Male;
    Middle Age; Parkinson Disease DT; Selegiline TU
IS- 0065-1427
EM- 9005

TI- Selegiline in the early and late phases of Parkinson's disease.
AU- Csanda E; T´arczy M
AD- Institute of Neurology, Semmelweis Medical University, Budapest,
    Neural Transm Suppl, 25(-HD-):105-13  1987
AB- Selegiline is a useful adjuvant drug in the treatment of Parkinson's
    disease. In the early phase selegiline can be given in monotherapy. Its
    effect is not always sufficient to eliminate all the symptoms. In spite
    of this observation the administering of selegiline as monotherapy can be
    useful because in case of the immediate introduction of levodopa therapy
    untoward effects may appear in an early stage of treatment. In the course
    of substitution therapy selegiline successfully replaces about 30% of
    levodopa administered in "de novo" parkinsonian patients. Selegiline has
    a favourable beneficial effect in reducing the mild forms of response
    fluctuations. The addition of selegiline in such patients to the
    continuing substitution therapy prevents the development of more severe
    "on-off" manifestations. In severely disabled patients with irregular
    response swings or permanent akinesia the use of selegiline as an
    adjuvant drug cannot modify anymore the course of the disease.
LA- Eng
UI- 88117472
MM- Parkinson Disease DT; Phenethylamines TU; Selegiline TU
NN- Disability Evaluation; Dopa AD; Dopa TU; Human; Parkinson Disease PP;
    Time Factors
IS- 0303-6995
EM- 8805

TI- Selegiline in narcolepsy.
AU- Roselaar SE; Langdon N; Lock CB; Jenner P; Parkes JD
AD- University Department of Neurology, King's College School of Medicine,
    London, England.
SR- Sleep,
    10(5):491-5  1987 Oct
AB- We examined the effect of the specific monoamine oxidase-B (MAO-B)
    inhibitor selegiline (deprenyl, Eldepryl), 20-30 mg p.o. daily, in 21
    subjects with the narcoleptic syndrome for 4 weeks. Selegiline was
    compared to no treatment (7 subjects) or conventional central stimulant
    drugs, including dexamphetamine or mazindol (14 subjects). Severity and
    frequency of narcolepsy, accessory symptoms, and effects of selegiline on
    mood were measured. Selegiline, as well as causing MAO-B inhibition, is
    interconverted to amphetamine. Urinary amphetamine and methamphetamine
    excretion were determined in 18 subjects after 4 weeks on selegiline and
    the results were compared with amphetamine excretion in subjects on
    dexamphetamine. The effect of selegiline, 20-30 mg p.o., on alertness and
    mood was similar to that of dexamphetamine in the same dosage, with
    comparable sympathomimetic side effects. Selegiline, 20 mg p.o., caused a
    subjective increase in alertness for 4-8 h. Mean urinary amphetamine
    excretion on dexamphetamine, 15-70 mg daily (mean 29 mg) at pH 5.6-6.6,
    was 5,184 micrograms/24 h, and on selegiline, 20-30 mg daily (mean 22.5),
    was 4,127 micrograms/24 h. We conclude that selegiline, 20-30 mg daily,
    requires further evaluation in narcolepsy.
LA- Eng
UI- 88070095
MM- Cataplexy DT; Narcolepsy DT; Phenethylamines TU; Selegiline TU
NN- Adult; Affect DE; Aged; Comparative Study; Dextroamphetamine TU; Human;
    Male; Mazindol TU; Middle Age
IS- 0161-8105
EM- 8803

TI- Transmitter releasing action of selegiline ((-)-deprenyl) from
    peripheral sympathetic nerves under different experimental conditions.
AU- T¨or¨ok TL; Paul´o T; T´oth PT; Nguyen TT; Azzidani AM; Magyar K
AD- Department of Pharmacodynamics, Semmelweis University of Medicine,
    Budapest, Hungary.
    Pharm Pharmacol, 39(10):797-802  1987 Oct
AB- A high concentration of selegiline ((-)-deprenyl; 10(-4) M) potentiated
    low frequency (2 Hz) nerve stimulation-evoked release of
    [3H]noradrenaline from the isolated main pulmonary artery of the rabbit
    in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal
    (corticosterone, 5 X 10(-5) M) uptake blockers, and inhibited the
    postsynaptic response. The transmitter-releasing action of 10(-4) M
    selegiline was inhibited by a moderate increase of external K+ (23.6 mM).
    Excess K+ by itself abolished the nerve-evoked release of
    [3H]noradrenaline but did not increase the resting outflow of
    radioactivity. Excess Ca2+ (7.5 mM) increased the stimulation-evoked
    transmitter release. In the presence of excess Ca2+, selegiline (10(-4)
    M) was effective in increasing the [3H]noradrenaline release in response
    to nerve-stimulation. Excess Ca2+ partly antagonized the postsynaptic
    inhibitory action of selegiline. In Ca2+-free, 1 mM EGTA-containing Krebs
    solution both the nerve-evoked 3H release and the transmitter releasing
    action of selegiline were abolished in agreement with the
    'Ca-hypothesis'. The voltage-dependent K+-channel blocker,
    4-aminopyridine (10(-5) M), increased the nerve-stimulation-evoked
    release of tritium from arteries. If selegiline was also present in the
    perfusion medium the nerve-evoked transmitter release further increased.
    4-Aminopyridine completely antagonized the inhibitory action of
    selegiline on the postsynaptic contraction.
LA- Eng
UI- 88090382
MM- Neurotransmitters ME; Phenethylamines PD; Selegiline PD; Sympathetic
    Nervous System ME
NN- Animal; Calcium PH; Female; In Vitro; Ion Channels DE; Male; Muscle
    Contraction DE; Muscle, Smooth, Vascular IR; Muscle, Smooth, Vascular ME;
    Norepinephrine ME; Pulmonary Artery IR; Pulmonary Artery ME; Rabbits;
    Support, Non-U.S. Gov't; Sympathetic Nervous System DE
IS- 0022-3573
EM- 8804

TI- Selegiline in the treatment of Parkinson's disease.
AU- Heinonen EH; Rinne UK
AD- Department of Neurology, University of Turku, Finland.
SR- Acta
    Neurol Scand Suppl, 126(-EM-):103-11  1989
AB- Selegiline is a selective, irreversible inhibitor of monoamine oxidase
    type B (MAO-B). It also inhibits the reuptake of catecholamines into the
    presynaptic nerve and enhances the synthesis of dopamine by blocking the
    presynaptic dopamine autoreceptors. Thanks to these properties it
    potentiates and prolongs the duration of action of levodopa. Several
    clinical trials have shown its efficacy as an adjuvant to levodopa
    therapy. Improvement in parkinsonian disability and reduction of
    fluctuations in disability can be achieved by adding selegiline to the
    prevailing levodopa therapy. End-of-dose type fluctuations, in
    particular, react favourably to selegiline. Side-effects of the therapy
    can be managed by reducing the dose of levodopa. According to preliminary
    studies selegiline may also have some benefit as monotherapy in de novo
    parkinsonian patients. High doses of selegiline have been found to have
    some antidepressant efficacy, especially in patients with nonendogenous
    depression. It may also have an effect on bradyphrenia and some symptoms
    of cognitive dysfunction and dementia. In animal models selegiline has
    been shown to prevent parkinsonism caused by MPTP and also to increase
    the life span of rats. Whether selegiline slows down the progression of
    Parkinson's disease needs further examination.
LA- Eng
UI- 90143724
MM- Parkinson Disease DT; Phenethylamines TU; Selegiline TU
NN- Drug Therapy, Combination; Human; Levodopa TU; Selegiline AE
IS- 0065-1427
EM- 9005

TI- Selegiline as an adjunct to conventional levodopa therapy in Parkinson's
    disease. Experience with this type B monoamine oxidase inhibitor in 200
    patients [published erratum appears in Arch Neurol 1990 Feb;47(2):160
AU- Elizan TS; Yahr MD; Moros DA; Mendoza MR; Pang S; Bodian CA
AD- Department of Neurology, Mount Sinai Medical Center, City University of
    New York, NY 10029.
SR- Arch
    Neurol, 46(12):1280-3  1989 Dec
AB- Two hundred patients at a median age of 63 years, receiving conventional
    levodopa therapy for 8 years, who had had Parkinson's disease for 10
    years, tried a regimen of selegiline (L-deprenyl), a type B monoamine
    oxidase inhibitor, at a daily dose of 10 mg, for varying periods from
    less than 6 months to more than 24 months (28% over 24 months).
    Selegiline does improve parkinsonism during the initial 6 months to 12 to
    24 months of combined therapy in one third to almost half of patients
    with an end-of-dose type of response to long-term levodopa therapy.
    However, even this particular class of patients is unable to maintain
    such an improvement by 36 months, much less by 48 months, from the start
    of the selegiline trial. About one quarter of poor responders to levodopa
    and those with random deterioration show improvement in their
    parkinsonian status in the first 6 months of the selegiline trial, but
    their conditions quickly deteriorate by 1 year. The predominant pattern
    of response to previous levodopa therapy and the severity of the total
    disability score at the initiation of the selegiline trial were the two
    variables that were predictive of risk of failure with the drug. No
    evidence suggested that selegiline decreases the excess mortality rate of
    Parkinson's disease above that achieved with the use of levodopa alone.
    Selegiline as an adjunctive agent to conventional levodopa therapy was
    not unduly impressive with regard to preventing progression of
    Parkinson's disease.
LA- Eng
UI- 90073280
MM- Levodopa TU; Parkinson Disease DT; Phenethylamines TU; Selegiline TU
NN- Clinical Trials; Drug Therapy, Combination; Human; Middle Age; Parkinson
    Disease MO; Prospective Studies; Selegiline AD; Support, U.S. Gov't,
IS- 0003-9942
EM- 9003

TI- ["Widening horizons" in the clinical application of selegiline]
AU- Kov´acs A
AD- Chinoin Gy´ogyszer ´es Vegy´eszeti Term´ekek Gy´ara Rt., Budapest.
SR- Acta
    Pharm Hung, 62(5):259-64  1992 Sep
AB- The first paper on the beneficial effect of selegiline in the treatment
    of Parkinson's disease was published 17 years ago. In the first ten years
    several clinical studies were conducted world-wide to prove its efficacy
    as an adjuvant to the basic 1-dopa therapy. Although the design, duration
    and number of treated patients were different, the overall results were
    mainly uniform. The patients treated with 1-dopa selegiline combination
    showed marked improvement in disability, increasing duration of 1-dopa
    effect and marked lessening of dose-related fluctuations were seen,
    compared to those treated with 1-dopa alone. It became also generally
    evident that selegiline allows a 10-30% decrease in 1-dopa dose. The
    investigations in which selegiline has been used as monotherapy have been
    triggered by some purely clinical experience and by the discovery of
    pathobiochemical mechanisms of MPTP toxicity which causes fairly similar
    clinical picture to Parkinson's disease and can be successfully prevented
    by selegiline. The newly diagnosed parkinsonian patients treated with
    selegiline alone showed marked improvement in their clinical state.
    Beside the actual clinical effect on disability, selegiline slowed down
    the progression of Parkinson's disease. The latter fact has been proven
    in the largest clinical trial ever done with selegiline (DATATOP).
    Selegiline monotherapy can delay the need for 1-dopa substitution by
    around one year or longer. Based on the continuously growing clinical
    experiences it became widely accepted that selegiline is the drug of
    choice as initial treatment for newly diagnosed parkinsonian
LA- Hun
UI- 93142571
MM- Selegiline TU
NN- Alzheimer Disease DT; Drug Therapy, Combination; English Abstract;
    Human; Levodopa TU; Parkinson Disease DT
IS- 0001-6659
EM- 9304

TI- Toxicological detection of selegiline and its metabolites in urine using
    fluorescence polarization immunoassay (FPIA) and gas chromatography-mass
    spectrometry (GC-MS) and differentiation by enantioselective GC-MS of the
    intake of selegiline from abuse of methamphetamine or amphetamine.
AU- Maurer HH; Kraemer T
AD- Abteilung Toxikologie, Universit¨at des Saarlandes, Homburg, Federal
    Republic of Germany.
SR- Arch
    Toxicol, 66(9):675-8  1992
AB- Selegiline (R(-)-N-methyl-N-(1-phenyl-2-propyl)-2-propinylamine), a
    selective MAO-B inhibitor used as an antiparkinsonian, is excreted in
    urine as N-desmethyl selegiline (norselegiline), R(-)-methamphetamine
    (R(-)-MA), R(-)-amphetamine (R(-)-AM) and their conjugated p-hydroxy
    derivatives. We found that the fluorescence polarization immunoassays
    (FPIA) TDx amphetamine/methamphetamine II (AM/MA II) and TDx amphetamine
    class (AM class) lead to positive results for up to 2 days after a single
    oral dose of 10 mg selegiline (detection limit: 0.1 mg/l, each). Every
    urine specimen from long term selegiline patients (10 mg/day) showed
    positive TDx results during the selegiline regimen. Positive TDx results
    were confirmed using gas chromatography-mass spectrometry (GC-MS).
    Selegiline metabolites, particularly MA, could be detected in urine for
    up to 7 days after intake of a single oral dose of 10 mg selegiline
    (detection limit: 0.01 mg/l for MA and AM). Norselegiline, the only
    specific selegiline metabolite, was only detectable for about 12 h.
    Moreover, norselegiline was not detected in all urine samples from long
    term selegiline patients (10 mg/day). Since differentiation of selegiline
    intake from MA/AM abuse by detecting norselegiline was not possible in
    most cases, an enantioselective GC-MS procedure was developed. It allowed
    differentiation of the enantiomers of the selegiline metabolites and
    thereby separation of selegiline intake (only R(-)-enantiomers) from
    methamphetamine and/or amphetamine abuse (racemates or S(+)-enantiomers).
    After derivatization with S(-)-N-trifluoroacetyl-prolyl chloride (TPC),
    the two enantiomers of MA and AM were each separated as diastereomers
    employing the routinely used achiral GC capillary.(ABSTRACT TRUNCATED AT
    250 WORDS)
LA- Eng
UI- 93129125
MM- Amphetamine; Methamphetamine; Selegiline TO; Substance Abuse Detection
NN- Fluorescence Polarization Immunoassay; Human; Mass Fragmentography;
    Selegiline UR; Stereoisomerism
IS- 0340-5761
EM- 9304

TI- [Pharmacokinetics and metabolism of selegiline]
AU- Szatm´ari I; T´oth K
AD- Chinoin Gy´ogyszer ´es Vegy´eszeti Term´ekek Gy´ara Rt., Budapest.
SR- Acta
    Pharm Hung, 62(5):243-8  1992 Sep
AB- As it has been shown is animal experiments, selegiline administered
    orally is absorbed rapidly. The compound penetrates the blood-brain
    barrier and the concentration of selegiline and/or its metabolites is
    high in the brain. Selegiline is eliminated primarily by renal excretion
    (73%) and 14% of the dose is eliminated with faeces. The main metabolic
    pathway is N-dealkylation. N-demethyl-selegiline, amphetamine and
    methamphetamine are the main metabolites. p-Hydroxylated derivatives of
    amphetamine and methamphetamine could also be identified in rat urine.
    (-)-Selegiline gives rise to (-) metabolites and does not undergo
    racemization. Selegiline is bound to macromolecules extensively. The
    metabolites have lower affinity to plasma proteins than the parent drug
    do. Selegiline and its metabolites do not accumulate in the organism not
    even during prolonged administration.
LA- Hun
UI- 93142569
MM- Selegiline PK
NN- Animal; Blood Proteins ME; Brain ME; English Abstract; Human; Selegiline
IS- 0001-6659
EM- 9304

TI- [Pharmacology of selegiline (recent considerations)]
AU- Tardos L; J´anv´arin´e Kany´o E
AD- Chinoin Gy´ogyszer ´es Vegy´eszeti Term´ekek Gy´ara Rt., Budapest.
SR- Acta
    Pharm Hung, 62(5):237-41  1992 Sep
AB- The nigrostriatal system, where dopaminergic neuron activity dominates,
    plays and important role in control of motoric and psychic functions.
    Selegiline with its neurochemical activity ie. MAO-B enzyme and dopamine
    uptake inhibition is able to restore or improve the deteriorated function
    of that system. Selegiline can hinder the uptake of tyramine into the
    peripheral sympathetic nerve endings, so cheese effect, which is a
    characteristic and dangerous side effect induced by MAO-A inhibitors,
    does not occur. Selegiline can potentiate the learning activity of PEA in
    rats, these effect may be connected with increased dopamine turnover in
    the striatum. In pathological conditions dopamine can be replaced by
    L-dopa, so it has a fundamental role in the improvement of dopaminergic
    functions. According to neurochemical activity selegiline takes a
    prominent role in the extension and improvement of L-dopa therapy. The
    neuroprotective effect of selegiline is multiple, with the inhibition of
    MAO-B it can stop the production of neurotoxin MPP+ (arising from MPTP)
    and its uptake into the nerve endings respectively. In chronic treatment
    with Selegiline SOD activity increases in rats, as a consequence the
    level of free oxygen radicals and toxic metabolites can be diminished.
    Chronic treatment with selegiline does not influence the activity of
    young animals, but improves sexual activity and learning capacity and
    enlarges life expectancy of old rats. These experiments verified its
    positive activity on the nigrostriatal system and give a good chance for
    geriatric usage. In longtime treatments dependency was not stated.
LA- Hun
UI- 93142568
MM- Selegiline PD
NN- Age Factors; Animal; Dose-Response Relationship, Drug; English Abstract;
    Mice; Neurotransmitter Uptake Inhibitors PD; Rats; Sex Behavior, Animal
    DE; Tyramine PH
IS- 0001-6659
EM- 9304

TI- An interim report of the effect of selegiline (L-deprenyl) on the
    progression of disability in early Parkinson's disease. The Parkinson
    Study Group.
AU- Shoulson I
AD- Department of Neurology, University of Rochester Medical Center, NY
SR- Eur
    Neurol, 32 Suppl 1(-AU-):46-53  1992
AB- The pathogenesis of Parkinson's disease (PD) has been linked to
    oxidative-mediated events including increased monoamine oxidase (MAO) and
    free-radical generation. We are investigating the ability of the MAO
    inhibitor, selegiline (deprenyl), and of the free-radical scavenger,
    tocopherol, to delay the onset of disability requiring levodopa therapy
    (primary end point) in patients with early PD. Eight hundred patients
    with early, untreated PD were enrolled in the multi-center
    placebo-controlled, double-blind clinical trial 'Deprenyl and Tocopherol
    Antioxidative Therapy of Parkinsonism (DATATOP)'. Subjects were assigned
    by 2 x 2 factorial design to receive selegiline (10 mg/day), tocopherol
    (2,000 IU/day), a combination of both drugs, or placebo, and followed to
    determine if and when disability occurred requiring levodopa therapy.
    After 12 +/- 5 months of observation, independent monitoring prompted a
    preliminary analysis indicating that selegiline 10 mg/day significantly
    extended the time to the primary end point. Selegiline therapy, alone or
    in combination with tocopherol, resulted in a 57% reduction in the rate
    of developing disability requiring levodopa therapy (p < 10(-10)) and a
    50% reduction in the rate of loss of full-time employment (p = 0.01).
    Deterioration of motor and mental features was significantly less in
    selegiline-treated subjects. Adverse effects were minor and infrequent.
    We conclude from these preliminary results that selegiline (10 mg/day)
    delays the onset of disability associated with early, otherwise untreated
    PD. It remains unclear whether these benefits derive from mechanisms that
    are symptomatic (dopaminergic), protective (anti-neurotoxic), or both.
    The DATATOP study is ongoing to examine the long-term effects of
    selegiline and the independent and interactive effects of tocopherol.
LA- Eng
UI- 93049491
MM- Disability Evaluation; Parkinson Disease DT; Selegiline TU
NN- Activities of Daily Living; Adult; Aged; Comparative Study; Double-Blind
    Method; Female; Follow-Up Studies; Human; Long-Term Care; Male; Middle
    Age; Neurologic Examination DE; Selegiline AE; Support, Non-U.S. Gov't;
    Support, U.S. Gov't, P.H.S.; Vitamin E AE; Vitamin E TU
IS- 0014-3022
EM- 9302

TI- [Long-term selegiline tolerance in the treatment of Parkinson's disease]
AU- Vermersch P; Petit H
AD- Clinique Neurologique, CHU de Lille.
SR- Therapie,
    47(1):75-8  1992 Jan-Feb
AB- Tolerability is one of the main problems of the long-term use of
    antiparkinsonian drugs, especially in the advanced stages of Parkinson's
    disease. Since 1988, we have performed a prospective study to assess the
    clinical and therapeutic factors which may influence the tolerability of
    a new antiparkinsonian drug, selegiline. 168 patients, with a mean age of
    68, were treated with selegiline in combination with L-Dopa or with
    L-Dopa and a dopamine agonist (bromocriptine, lisuride or piribedil).
    After an average of 19 months, 23 adverse effects (13.7%) were noted
    during the first three months of treatment with selegiline.
    Discontinuation was required in only 10 cases (5.9%) with 9 out of 10 for
    a psychotic episode. Neither age, nor the stage of the disease, nor the
    dose of levodopa in combination with selegiline or the presence of mental
    disturbances seemed to be predicting factors for appearance of a psychic
    episode. If selegiline with levodopa or with bromocriptine and levodopa
    appeared to be safe antiparkinsonian combinations, significant psychic
    side effects occurred with piribedil in combinations with selegiline and
    levodopa. A possible explanation was that selegiline potentiates
    piribedil side-effects.
LA- Fre
UI- 92397257
MM- Parkinson Disease DT; Selegiline TU
NN- Aged; Drug Tolerance; English Abstract; Female; Human; Long-Term Care;
    Male; Parkinson Disease EP; Prospective Studies; Selegiline AE
IS- 0040-5957
EM- 9212

TI- Selegiline--an overview of its role in the treatment of Parkinson's
AU- Wessel K; Szelenyi I
AD- Medizin Deutschland, Frankfurt/Main.
SR- Clin
    Investig, 70(5):459-62  1992 May
AB- Selegiline (10 mg per day) selectively inhibits monoamine oxidase type B
    and thus thwarts the metabolism of dopamine by this enzyme. Selegiline
    has been used in the therapy of Parkinson's disease since 1986. It
    enhances the efficacy of levodopa, allows a reduction of the levodopa
    dose, and improves fluctuations in disability. It also interacts with
    mechanisms suspected of playing a role in the progression of the disease.
    Animal studies have shown that selegiline prevents the development of a
    Parkinson-like syndrome induced by the neurotoxin MPTP. It decreases
    oxidative stress resulting from the metabolism of dopamine via MAO-B.
    Clinical studies have shown that selegiline is effective in the therapy
    of untreated de novo patients: the progression of symptoms demanding the
    introduction of levodopa into the therapy was delayed, and the risk of
    needing levodopa treatment within one year was reduced by 57% with
    selegiline. The mode of action of this drug in the treatment of early
    Parkinson's disease is still under discussion. There is strong evidence
    that selegiline may slow the progression of the disease, but a direct
    symptomatic effect cannot be excluded.
LA- Eng
UI- 92288576
MM- Parkinson Disease DT; Selegiline TU
NN- Human; Monoamine Oxidase ME; Parkinson Disease ME; Selegiline PD;
    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ME
IS- 0941-0198
EM- 9209

TI- Selegiline as initial treatment in de novo parkinsonian patients.
AU- Myllyl¨a VV; Sotaniemi KA; Vuorinen JA; Heinonen EH
AD- Department of Neurology, Oulu University Central Hospital, Finland.
SR- Neurology,
    42(2):339-43  1992 Feb
AB- To investigate the efficacy and safety of selegiline in the early phase
    of Parkinson's disease (PD), we carried out a placebo-controlled,
    double-blind, parallel trial. De novo PD patients were randomized to
    receive either selegiline (10 mg/d) or matching placebo. We continued
    selegiline or placebo until levodopa therapy became necessary and
    assessed the disability using three different rating scales at baseline,
    after 3 weeks, at 2, 4, 8, and 12 months, and at every 4 months
    thereafter. Fifty-two patients were eligible for the analysis, 27 in the
    selegiline group and 25 in the placebo group. The median duration of time
    before levodopa had to be initiated was 545 +/- 90 days with selegiline
    and 372 +/- 28 days with placebo (p = 0.03). Disability was significantly
    less in the selegiline group than in the placebo group up to 12 months.
    The period of time during which the mean total Columbia University Rating
    Scale score stayed below the baseline was used to express the initial
    symptomatic effect of the treatments. The difference in this initial
    improvement time between the two groups was about 3 months and did not
    alone explain the difference in the delay of the need to start levodopa
    therapy. Selegiline was well tolerated and there were no severe side
    effects. We conclude that selegiline delays the need to start levodopa in
    de novo PD patients, has symptomatic efficacy, and possibly retards the
    progression of the disease.
LA- Eng
UI- 92140655
MM- Parkinson Disease DT; Selegiline TU
NN- Aged; Double-Blind Method; Drug Evaluation; Female; Human; Male; Middle
    Age; Selegiline AE
IS- 0028-3878
EM- 9205

TI- A review of the pharmacology of selegiline.
AU- Heinonen EH; Lammintausta R
AD- Orion Corporation Farmos, Research and Development, Turku, Finland.
SR- Acta
    Neurol Scand Suppl, 136(Heinonen EH):44-59  1991
AB- Selegiline (1-deprenyl) is an irreversible inhibitor of monoamine
    oxidase (MAO) type B. Because in the human brain, dopamine is metabolised
    mainly by MAO-B, selegiline increases dopamine content in the central
    nervous system. Besides the inhibition of MAO-B, selegiline also inhibits
    the uptake of dopamine and noradrenaline into presynaptic nerve and
    increases the turnover of dopamine. Thanks to these properties,
    selegiline significantly potentiates the pharmacological effects of
    levodopa. These favourable characteristics have been applied in the
    treatment of Parkinson's disease using selegiline both with levodopa and
    alone. Unlike earlier MAO-inhibitors, selegiline does not potentiate the
    hypertensive effects of tyramine. This is due to the selectivity to
    MAO-B, leaving intestinal MAO-A intact, and also due to the fact that
    selegiline inhibits the uptake of tyramine into neurons. Selegiline can
    prevent the parkinsonism caused by MPTP in animals; similar findings have
    been reported with other toxins like 6-OHDA and DSP-4, that destroys
    noradrenergic nuclei. Furthermore, selegiline reduces oxidative stress
    caused by degradation of dopamine and increases free radical elimination
    by enhancing superoxide dismutase and catalase activity. These findings
    may be important when considering the possible neuroprotective effects of
    selegiline. Besides the basic pharmacology also the interactions and
    pharmacokinetics of selegiline are reviewed in this article.
LA- Eng
UI- 92197287
MM- Parkinson Disease DT; Parkinson Disease EN; Selegiline PK; Selegiline TU
NN- Animal; Brain DE; Brain EN; Dose-Response Relationship, Drug; Drug
    Interactions; Human; Isoenzymes BL; Levodopa AE; Levodopa PK; Levodopa
    TU; Monoamine Oxidase BL; Neurotransmitters BL; Parkinson Disease MO;
    Selegiline AE; Survival Rate
IS- 0065-1427
EM- 9206

TI- Selegiline as a primary treatment of Parkinson's disease.
AU- Myllyl¨a VV; Sotaniemi KA; Vuorinen JA; Heinonen EH
AD- Department of Neurology, University of Oulu, Finland.
SR- Acta
    Neurol Scand Suppl, 136(-VI-):70-2  1991
AB- In order to investigate the efficacy of selegiline as a primary
    treatment in Parkinson's disease (PD), we carried out a placebo
    controlled, double-blind prospective trial. Fifty-four de novo patients
    with PD were randomized to receive either selegiline (10 mg/day) or
    matching placebo. We continued the monotherapy until the initiation of
    levodopa therapy became necessary. The disability of the patients was
    evaluated with three different rating scales at baseline, after 3 weeks,
    2, 4, 8, and 12 months, and every 4 months thereafter. Fifty-two patients
    were eligible for the final analysis: 27 in the selegiline group and 25
    in the placebo group. The median duration of time without levodopa was
    545 +/- 90 days in the selegiline treated patients and 372 +/- 28 days in
    the placebo treated ones (p = 0.03). The disability of the patients was
    significantly milder in the selegiline than in the placebo group up to 12
    months. More patients showed symptomatic improvement in the selegiline
    than in the placebo group. However, the symptomatic effect alone did not
    explain the prolongation of the time without levodopa in the selegiline
    treated patients. Selegiline was well tolerated and no severe side
    effects were encountered.
LA- Eng
UI- 92197291
MM- Parkinson Disease DT; Selegiline TU
NN- Activities of Daily Living; Double-Blind Method; Human; Neurologic
    Examination DE; Prospective Studies; Selegiline AE
IS- 0065-1427
EM- 9206

TI- Selegiline. A review of its pharmacology, symptomatic benefits and
    protective potential in Parkinson's disease.
AU- Chrisp P; Mammen GJ; Sorkin EM
AD- Adis Drug Information Services, Auckland, New Zealand.
SR- Drugs
    Aging, 1(3):228-48  1991 May
AB- Selegiline (deprenyl) is a selective inhibitor of cerebral monoamine
    oxidase type B at the dosage (10 mg/day) used in patients with
    Parkinson's disease. Through this activity, the drug increases
    nigrostriatal dopamine levels, and may protect neurons against damage by
    free radicals and possibly exogenous neurotoxins. Selegiline also
    inhibits dopamine reuptake from the synaptic cleft. Because of its
    selectivity, selegiline 10mg daily does not prevent the breakdown and
    exacerbate the indirect pressor effects of dietary amines such as
    tyramine; it is devoid of the 'cheese' effect. Following oral
    administration, selegiline is rapidly metabolised to L-methamphetamine
    and L-amphetamine, which may account for the euphoria and insomnia seen
    in many patients, although potentiation of dopaminergic activity with
    concurrent levodopa appears more likely. The drug is a useful adjunct to
    levodopa in Parkinsonism, improving 'end-of-dose' fluctuations, producing
    modest improvements in motor function, and allowing a reduction in
    levodopa dosage. Indeed, if levodopa dosages are not decreased when
    selegiline is added to the therapeutic regimen, peak concentration
    dyskinesias due to levodopa are often exacerbated. However, symptomatic
    benefits are rarely maintained for more than a year and selegiline is
    relatively ineffective in allaying the abrupt swings in response to
    levodopa ('on/off' effects). When used alone in patients with mild
    disease, selegiline appears to slow the rate of symptom progression and
    may extend survival, through either neuroprotection or symptom relief.
    Whichever mechanism(s) is responsible, there is strong evidence to
    suggest that selegiline should be considered both in patients newly
    diagnosed with Parkinson's disease in an attempt to delay symptom
    progression, and in those experiencing dose-dependent fluctuations in
    response to levodopa.
LA- Eng
UI- 92173436
MM- Parkinson Disease DT; Selegiline TU
NN- Adult; Aged; Animal; Drug Interactions; Human; Middle Age; Selegiline
    PD; Selegiline PK
IS- 1170-229X
EM- 9206

TI- Stereoselective analyses of selegiline metabolites: possible urinary
    markers for selegiline therapy.
AU- Hasegawa M; Matsubara K; Fukushima S; Maseda C; Uezono T; Kimura K
AD- Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
SR- Forensic
    Sci Int, 101(2):95-106  1999 Apr 26
AB- The stereoselective analysis of selegiline metabolites in human urine
    and plasma by gas chromatography using the chiral column with the
    non-chiral reagent was investigated for the differentiation of selegiline
    therapy from the methamphetamine (MA) abuse. This method gave clear
    separations of MA and amphetamine (AM) isomers without any artifactual
    optical-opposite peaks due to the reagent. After the administration of
    selegiline tablets, desmethylselegiline (DMS), MA and AM were observed as
    (-)-isomers in the urine and plasma. Within the first 48 h after dosing,
    approximately 40% of selegiline administered was excreted in urine as
    these three metabolites. The parent drug, selegiline, was not detected in
    any urine or plasma samples. On the other hand, MA and AM were observed
    only as (+)-isomers in the urine of MA abusers. For the distinction of
    selegiline users from street MA abusers in urinalysis, (-)-DMS, a
    specific metabolite of selegiline, was not a suitable marker. (-)-DMS
    rapidly disappeared from urine and was excreted only 1% of the given
    dose. By the moment analysis with the trapezoidal integration, the mean
    residence times of (-)-DMS in plasma and urine were 2.7 and 3.8 h,
    respectively, which were 5-20 times shorter than those of (-)-MA or
    (-)-AM. The values of AM/MA in the urine increased from 0.24 to 0.67 (r =
    0.857) along with time after the selegiline administration. This ratio
    was not a sufficient marker to differentiate selegiline users from MA
    abusers, although the values of AM/MA in 74% of MA abusers were less than
    0.24. The present GC technique improved the chiral analyses of MA and AM.
    This chiral analysis is the most useful technique to avoid the
    misinterpretation in the discrimination between clinical selegiline
    therapy and illicit MA use.
LA- Eng
UI- 99299179
MM- Monoamine Oxidase Inhibitors ME; Selegiline ME; Selegiline TU
NN- Adult; Amphetamine UR; Amphetamines UR; Biological Markers;
    Chromatography, Gas; Diagnosis, Differential; Female; Human; Male;
    Methamphetamine UR; Middle Age; Monoamine Oxidase Inhibitors TU;
    Stereoisomerism; Substance Abuse Detection; Substance-Related Disorders
    DI; Substance-Related Disorders UR; Support, Non-U.S. Gov't
IS- 0379-0738
EM- 9909

TI- Effect of selegiline and desmethyl-selegiline on cortical electric
    activity in rats.
AU- Nickel B; Borbe HO; Szelenyi I
AD- Department of Pharmacology, ASTA Pharma AG, Frankfurt/Main, Federal
    Republic of Germany.
    Neural Transm Suppl, 32(Selegiline PD
AB- The pharmaco-EEG changes caused by the monoamine oxidase (MAO) B
    inhibitor selegiline were compared with the frequency band alterations
    aroused by its desmethyl metabolite after oral administration in rats.
    After single administration (5 mg/kg) the EEG changes caused by
    selegiline or desmethyl-selegiline differed significantly. Distinct
    decreases in delta and clear increases in theta EEG frequency bands were
    obvious after administration of selegiline. The single oral dose of
    desmethyl-selegiline (5 mg/kg) caused only trendly the same EEG changes
    observed after giving the mother compound. Following repeated
    administration on four consecutive days no significant differences in the
    frequency band changes could be seen after selegiline or
    desmethyl-selegiline. Based on present results it is likely that the mode
    of action of desmethyl-selegiline appears to be similar or identical with
    the mode of action of the parent compound, selegiline.
LA- Eng
UI- 91210713
MM- Amphetamines PD; Cerebral Cortex DE; Electroencephalography; Selegiline
NN- Animal; Female; Fourier Analysis; Rats; Rats, Inbred Strains
IS- 0303-6995
EM- 9108

TI- Selegiline effects on cocaine-induced changes in medial temporal lobe
    metabolism and subjective ratings of euphoria.
AU- Bartzokis G; Beckson M; Newton T; Mandelkern M; Mintz J; Foster JA; Ling
    W; Bridge TP
AD- Psychiatry Service, Little Rock VA Medical Center, AR 72114, USA.
SR- Neuropsychopharmacology,
    20(6):582-90  1999 Jun
AB- To test the effect of selegiline, a specific monoamine oxidase B (MAO-B)
    inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine
    in experienced users, eight cocaine-dependent (CD) subjects were
    evaluated using a within-subjects design. Each subject participated in
    two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography
    (PET) scans (baseline scan followed 24 h later by a second scan obtained
    in conjunction with a 40-mg cocaine infusion) performed before and after
    a 1-week period of daily treatment with 10 mg selegiline administered
    orally. The hippocampus and amygdala were evaluated because of their
    hypothesized involvement in the addiction process, and the thalamus was
    evaluated as a comparison region. Following 7 days of selegiline
    treatment, the magnitude of the subjective euphoria ("high") produced by
    cocaine infusion was reduced by 40% (cocaine by selegiline interaction F
    = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose
    utilization (normalized against whole brain counts) in the two limbic
    regions, but not the thalamus. In the amygdala, the effects of cocaine
    differed, depending upon whether or not patients were being treated with
    selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p =
    .043). A different effect was observed in the hippocampus, where
    selegiline treatment decreased metabolic activity irrespective of whether
    cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The
    concomitant changes in both the subjective experience of the "high" and
    normalized amygdala glucose utilization after selegiline treatment,
    suggest that a relationship exists between cocaine-induced euphoria and
    limbic metabolism. The data suggest that selegiline may be a useful
    adjunct in the treatment of cocaine dependence.
LA- Eng
UI- 99259411
MM- Brain DE; Cocaine PD; Cocaine-Related Disorders ME; Euphoria DE;
    Monoamine Oxidase Inhibitors PD; Selegiline PD
NN- Adult; Amygdaloid Body DE; Amygdaloid Body ME; Female; Glucose ME;
    Hippocampus DE; Hippocampus ME; Human; Magnetic Resonance Imaging; Male;
    Middle Age; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.;
    Support, U.S. Gov't, P.H.S.; Temporal Lobe DE; Temporal Lobe ME; Temporal
    Lobe RI; Thalamus DE; Thalamus ME; Tomography, Emission-Computed
IS- 0893-133X
EM- 9908

TI- Selegiline-induced postural hypotension in Parkinson's disease: a
    longitudinal study on the effects of drug withdrawal.
AU- Churchyard A; Mathias CJ; Lees AJ
AD- Institute of Neurology and University Department of Clinical Neurology,
    National Hospital for Neurology and Neurosurgery, London, UK.
SR- Mov
    Disord, 14(2):246-51  1999 Mar
AB- OBJECTIVES: The United Kingdom Parkinson's Disease Research Group
    (UKPDRG) trial found an increased mortality in patients with Parkinson's
    disease (PD) randomized to receive 10 mg selegiline per day and L-dopa
    compared with those taking L-dopa alone. Recently, we found that therapy
    with selegiline and L-dopa was associated with selective systolic
    orthostatic hypotension which was abolished by withdrawal of selegiline.
    This unwanted effect on postural blood pressure was not the result of
    underlying autonomic failure. The aims of this study were to confirm our
    previous findings in a separate cohort of patients and to determine the
    time course of the cardiovascular consequences of stopping selegiline in
    the expectation that this might shed light on the mechanisms by which the
    drug causes orthostatic hypotension. METHODS: The cardiovascular
    responses to standing and head-up tilt were studied repeatedly in PD
    patients receiving selegiline and as the drug was withdrawn. RESULTS:
    Head-up tilt caused systolic orthostatic hypotension which was marked in
    six of 20 PD patients on selegiline, one of whom lost consciousness with
    unrecordable blood pressures. A lesser degree of orthostatic hypotension
    occurred with standing. Orthostatic hypotension was ameliorated 4 days
    after withdrawal of selegiline and totally abolished 7 days after
    discontinuation of the drug. Stopping selegiline also significantly
    reduced the supine systolic and diastolic blood pressures consistent with
    a previously undescribed supine pressor action. CONCLUSION: This study
    confirms our previous finding that selegiline in combination with L-dopa
    is associated with selective orthostatic hypotension. The possibilities
    that these cardiovascular findings might be the result of non-selective
    inhibition of monoamine oxidase or of amphetamine and metamphetamine are
LA- Eng
UI- 99190038
MM- Antiparkinson Agents AE; Hypotension, Orthostatic CI; Parkinson Disease
    DT; Selegiline AE; Substance Withdrawal Syndrome PP
NN- Aged; Analysis of Variance; Blood Pressure DE; Dizziness CI; Drug
    Therapy, Combination; Epinephrine BL; Female; Head; Heart Rate DE; Human;
    Male; Middle Age; Norepinephrine BL; Posture PH; Prospective Studies;
    Severity of Illness Index; Time Factors
IS- 0885-3185
EM- 9908

TI- Dose linearity study of selegiline pharmacokinetics after oral
    administration: evidence for strong drug interaction with female sex
AU- Laine K; Anttila M; Helminen A; Karnani H; Huupponen R
AD- Department of Pharmacology and Clinical Pharmacology, University of
    Turku, Finland.
SR- Br
    J Clin Pharmacol, 47(3):249-54  1999 Mar
AB- AIMS: The purpose of this study was to characterize the dose
    relationship of selegline and desmethylselegiline pharmacokinetics within
    the selegiline dose range from 5 to 40 mg. METHODS: Eight female
    subjects, of whom four were using oral contraceptives, ingested a single
    dose of 5 mg, 10 mg, 20 mg or 40 mg of selegiline HCl in an open
    four-period randomized study. Concentrations of selegiline and
    desmethlylselegiline in serum were measured by gas chromatography for 5
    h. As it became evident that the use of oral steroids had a drastic
    effect on selegiline concentrations, the pharmacokinetic analyses were
    performed separately for oral contraceptive users and those not receiving
    any concomitant medication. RESULTS: The total AUC and Cmax of selegiline
    were 10-to 20-fold higher in those subjects taking oral steroids compared
    with subjects with no concomitant medication; this finding was consistent
    and statistically significant at all the four dose levels. The dose
    linearity of selegiline pharmacokinetics failed to be demonstrated in
    both groups. The AUC and Cmax of desmethylselegiline were only moderately
    higher (about 1.5-fold; P=NS at each dose level) in the subjects taking
    oral steroids than in those not receiving concomitant medication. The AUC
    values of desmethylselegiline increased in a dose linear manner in
    subjects with no concomitant medication, but not in the oral steroid
    group. The metabolic ratio (AUC(desmethylselegiline)/AUC(selegiline)) was
    several-fold lower in the group receiving oral steroids compared with the
    no-concomitant-medication group (P<0.005 at all the four dose levels).
    CONCLUSIONS: Concomitant use of oral contraceptives caused a drastic
    (20-fold) increase in the oral bioavailability of selegiline. The highly
    significant difference in the metabolic ratio between the groups provides
    evidence that the mechanism of the interaction between selegiline and
    female sex steroids involves reduced T-demethylation of selegiline. The
    present results suggest that concomitant use of selegiline with exogenous
    female sex steroids should be avoided or the dosage of selegiline should
    be reduced in order to minimize the risks of selegiline related adverse
    drug reactions.
LA- Eng
UI- 99233285
MM- Antiparkinson Agents PK; Contraceptive Agents, Female PD; Selegiline PK
NN- Administration, Oral; Adult; Amphetamines BL; Area Under Curve;
    Dose-Response Relationship, Drug; Drug Interactions; Female; Human;
    Selegiline BL
IS- 0306-5251
EM- 9908

TI- Effect of low-dose treatment with selegiline on dopamine transporter
    (DAT) expression and amphetamine-induced dopamine release in vivo.
AU- Lamensdorf I; Porat S; Simantov R; Finberg JP
AD- Rappaport Faculty of Medicine, Technion, Haifa, Israel.
SR- Br
    J Pharmacol, 126(4):997-1002  1999 Feb
AB- 1. Chronic treatment with low doses of the selective monoamine oxidase
    (MAO) type B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes
    elevation in extracellular level of 3,4-dihydroxyphenylethylamine
    (dopamine) in the rat striatum in vivo (Lamensdorf et al., 1996). The
    present study was carried out to determine whether this effect of
    selegiline could be the result of an inhibition of the high-affinity
    dopamine neuronal transport process. 2. Changes in activity of the
    dopamine transporter (DAT) in vivo following selegiline treatment were
    evaluated indirectly by microdialysis technique in the rat, from the
    change in striatal dopamine extracellular concentration following
    systemic amphetamine administration (4 mg kg(-1), i.p.). Striatal levels
    of the DAT molecule were determined by immunoblotting. Uptake of
    [3H]-dopamine was determined in synaptosomes from selegiline-treated
    animals. 3. Amphetamine-induced increase in striatal extracellular
    dopamine level was attenuated by one day and by chronic (21 days)
    treatment with selegiline (0.25 mg kg(-1), s.c.). 4. Striatal levels of
    DAT were elevated after 1 and 21 days treatment with selegiline, but were
    not affected by clorgyline, rasagiline, nomifensine or amphetamine. 5.
    The increase in DAT expression, and attenuation of amphetamine-induced
    dopamine release, were not accompanied by a change in [3H]-dopamine
    uptake in synaptosomes of selegiline-treated animals. 6. The results
    suggest that a reversible inhibition of dopamine uptake occurs following
    chronic low dose selegiline treatment in vivo which may be mediated by an
    increase in endogenous MAO-B substrates such as 2-phenylethylamine,
    rather than by the inhibitor molecule or its metabolites. Increased DAT
    expression appears to be a special property of the selegiline molecule,
    since it occurs after one low dose of selegiline, and is not seen with
    other inhibitors of MAO-A or MAO-B. The new DAT molecules formed
    following selegiline treatment appear not to be functionally active.
LA- Eng
UI- 99208123
MM- Amphetamine PD; Carrier Proteins DE; Dopamine SE; Monoamine Oxidase
    Inhibitors PD; Selegiline PD
NN- Animal; Male; Microdialysis; Rats; Rats, Sprague-Dawley;
    3,4-Dihydroxyphenylacetic Acid ME DIHYDROXYPHENYLACETIC ACID 03 04
IS- 0007-1188
EM- 9907

TI- Is 10 milligrams selegiline essential as an adjunct therapy for the
    symptomatic treatment of Parkinson's disease?
AU- Mahmood I
AD- Office of Clinical Pharmacology and Biopharmaceutics, Division of
    Pharmaceutical Evaluation I, Food and Drug Administration, Rockville,
    Maryland 20852, USA.
SR- Ther
    Drug Monit, 20(6):717-21  1998 Dec
AB- Selegiline is used as an adjunct to levodopa in the symptomatic
    treatment of Parkinson's disease (PD). The normal daily dose of
    selegiline is 10 mg administered orally. This study, based on monoamine
    oxidase-B (MAO-B) inhibition, investigates whether a reduction in
    selegiline dose can provide the same beneficial effects seen with a 10-mg
    dose. The inhibition of platelet MAO-B activity against multiple dosing
    of selegiline (2.5, 5, and 7.5 mg) was predicted from the data obtained
    from literature (0.5, 1.0, 1.5, and 10 mg). A
    pharmacokinetic-pharmacodynamic model for selegiline was also developed.
    The data suggested that by 96 hours (four doses) the inhibition of
    platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg
    selegiline, whereas it takes only 48 hours (two doses) for doses of 5 mg
    and 7.5 mg to achieve this degree of inhibition. The
    pharmacokinetic-pharmacodynamic model was best described by a sigmoidal
    Emax model with an effect compartment. Based on the inhibition of MAO-B
    activity, a reduction in daily oral dose of selegiline appears possible
    without compromising the therapeutic effect. Therefore, lower doses of
    selegiline should be tested in clinical trials.
LA- Eng
UI- 99068883
MM- Monoamine Oxidase ME; Monoamine Oxidase Inhibitors AD; Parkinson Disease
    DT; Selegiline AD
NN- Blood Platelets ME; Chemotherapy, Adjuvant; Dose-Response Relationship,
    Drug; Drug Administration Schedule; Human; Levodopa TU; Monoamine Oxidase
    Inhibitors PK; Selegiline PK
IS- 0163-4356
EM- 9907

TI- CYP2D6 polymorphism is not crucial for the disposition of selegiline.
AU- Scheinin H; Anttila M; Dahl ML; Karnani H; Nyman L; Taavitsainen P;
    Pelkonen O; Bertilsson L
AD- Department of Clinical Pharmacology, Karolinska Institute, Huddinge
    University Hospital, Finland.
SR- Clin
    Pharmacol Ther, 64(4):402-11  1998 Oct
AB- OBJECTIVE: To determine the possible impact of CYP2D6 polymorphism on
    the pharmacokinetics and pharmacodynamics of selegiline. METHODS: Five
    poor metabolizers and 8 extensive metabolizers of debrisoquin (INN,
    debrisoquine) were given 10 mg selegiline hydrochloride. The
    concentrations of selegiline and its main metabolites in serum were
    determined for 4 days. The pharmacodynamics were quantitated by measuring
    platelet monoamine oxidase type B activity for 3 weeks. In addition, the
    effect of selegiline and its main metabolites on the CYP2D6-catalyzed
    dextromethorphan O-demethylase activity and the effect of quinidine on
    the metabolism of selegiline were studied in human liver microsomes.
    RESULTS: Peak serum concentrations of selegiline were reached rapidly and
    ranged from 1 to 32 nmol/L. The metabolite concentrations were
    considerably higher and remained so for a longer period. There were no
    significant differences in the pharmacokinetic parameters of selegiline,
    desmethylselegiline, and l-amphetamine between poor metabolizers and
    extensive metabolizers. However, the area under the serum
    concentration-time curve (AUC) values of l-methamphetamine were, on
    average, 46% higher (P = .01) in poor metabolizers than in extensive
    metabolizers. No significant correlations were found between debrisoquin
    metabolic ratio and AUC values of selegiline or its metabolites, except
    for l-methamphetamine (rs = 0.90; P < .001). The maximum monoamine
    oxidase type B inhibition was 97% in both groups. The inhibitory potency
    of selegiline, desmethylselegiline, and l-methamphetamine toward
    dextromethorphan O-demethylase was very low (50% inhibitory concentration
    values from 160 to 580 mumol/L). Quinidine (< or = 100 mumol/L) did not
    inhibit the formation of desmethylselegiline or l-methamphetamine from
    selegiline. CONCLUSIONS: CYP2D6 is not important in the primary
    elimination of selegiline, and the biological effect of selegiline seems
    to be similar in poor metabolizers and extensive metabolizers of
    debrisoquin. The inhibitory effect of selegiline and its main metabolites
    on CYP2D6 activity seems to be negligible.
LA- Eng
UI- 99014531
MM- Cytochrome P-450 CYP2D6GE CYTOCHROME P 450 CYP 002 D 006; Monoamine
    Oxidase Inhibitors PK; Selegiline PK
NN- Adrenergic Agents PK; Adult; Amphetamines PK; Area Under Curve;
    Debrisoquin PK; Female; Human; In Vitro; Male; Methamphetamine PK;
    Microsomes, Liver ME; Monoamine Oxidase Inhibitors BL; Polymorphism
    (Genetics); Reference Values; Selegiline BL; Support, Non-U.S. Gov't
IS- 0009-9236
EM- 9901
Copyright © 1999