Selegiline google search preview pane top right

Prescription drug
Consult a doctor if you have a medical concern.
Treats depression. This medicine is a monoamine oxidase (MAO) inhibitor.
Transdermal: Side effects - Warnings - How to use
By mouth: Side effects - Warnings - How to use
National Library of Medicine
Brand names: Emsam, Eldepryl, Zelapar
Molar mass: 187.281 g/mol
CAS ID: 14611-51-9
Pregnancy risk: Category C (Risk cannot be ruled out)
Drug classes: Monoamine oxidase inhibitor, Monoamine Oxidase Type B Inhibitor
Other drugs in same class: Rasagiline, Selegiline hydrochloride, More
May treat: Parkinson’s disease, Alzheimer’s disease, ADHD, Schizophrenia, Depressive Disorder

"… Selegiline, also known as l-deprenyl, is an irreversible and (relatively) selective

MAO-B inhibitor. Meta-analysis of published clinical trials confirms it offers a

cheap, safe and effective symptomatic treatment of early Parkinson’s disease.

Selegiline may also be neuroprotective and act as an antidepressant.

The enzyme monoamine oxidase has two main forms, type A and type B.

They are coded by separate genes. MAO may be inhibited with agents

that act reversibly or irreversibly; and selectively or unselectively.

These categories are not absolute. MAO type-A preferentially deaminates

serotonin and noradrenaline, and also non-selectively dopamine.

Type B metabolises dopamine, phenylethylamine (the chocolate amphetamine)

and various trace amines. At dosages up to around 10 mg or so daily,

selegiline retains its selectivity for the type-B MAO iso-enzyme;

but it is also a weak reversible inhibitor of the type-A MAO iso-enzyme.

In contrast to unselective and irreversible MAO inhibitors such as

tranylcypromine (Parnate) and phenelzine (Nardil), both of which strongly

potentiate the catecholamine-releasing effect of tyramine, selegiline inhibits

it. This ensures that low-dosage selegiline does not induce the hypertensive

“cheese effect”. A regimen of 2 x 5 mg daily of selegiline irreversibly inhibits

over 90% of MAO-B in the basal ganglia, the location of over 80% of

dopamine in the human brain. This level of MAO-B inhibition leads to a

40%-70% increase in synaptic dopamine. Selegiline has immune-system-boosting

and anti-neurodegenerative effects. Its use increases the level of tyrosine

hydroxylase, growth hormone, cerebral nitric oxide and the production of key

interleukins. Selegiline offers protection against DNA damage and oxidative

stress by hydroxyl and peroxyl radical trapping; and against excitotoxic

damage from glutamate. In addition, selegiline stimulates the release of

superoxide dismutase (SOD). SOD is a key enzyme which helps to quench

the production of damaging free-radicals. Potentially, selegiline may

prevent or reverse iron-induced memory impairment. The deposition of

excess iron in the brain is implicated several neurodegenerative diseases.

Selegiline protects the mitochondria via its effects on mitochondrial

membrane permeability: it directly interacts with the pore-forming structures.

Mitochondria are the energy powerhouses of the eukaryotic cell where

oxygen respiration occurs. If the mitochondrial theory of aging is correct,

then the root cause of aging is damage to mitochondrial DNA by free

radical leakage from adjacent respiratory proteins. Alas selegiline itself is

not an elixir of eternal youth. But its current “off-label” use by life-extensionists

prefigures the longevity-enhancing mitochondrial medicine of decades to come.

Taken consistently at low dosage, selegiline tends to extend the life-expectancy

of rats by some 20%; enhances drive, libido and endurance; and independently

improves cognitive performance in Alzheimer’s patients and in some healthy normals.

Its protective role against age-related memory decline derives at least in

part from its protection of hippocampal neurons in the aging brain.

Aging drug-free rats have poorer spatial memories and fewer hippocampal

neurons than their counterparts on selegiline. Selegiline is already

used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs.

Selegiline retards the metabolism not just of dopamine but also of phenylethylamine,

a trace amine also found in chocolate and released when we’re in love.

Selegiline protects the brain’s dopamine cells from oxidative stress. The brain

has only about 30-40 thousand dopaminergic neurons in all. We tend to

lose perhaps 13% a decade in adult life. An eventual 70%-80% loss

leads to the dopamine-deficiency disorder Parkinson’s disease, frequently

foreshadowed by depression. Selegiline in pill form was approved by

the FDA as an adjunct in the treatment of Parkinson’s disease in 1989.

In June 2006, the FDA approved once-daily orally disintegrating

tablets of selegiline HCl branded as Zelapar from Valeant Pharmaceuticals.

Zelapar is used as an adjunct therapy for Parkinsonians on levodopa/carbidopa

(Sinemet) whose response is deteriorating. The cocktail allegedly reduces

“off” time by an average of 2.2 hours per day. Administered at low doses,

selegiline is neuroprotective against possible damage to the serotonergic

fine axon terminals caused by overconsumption of the popular drug MDMA

(Ecstasy). Several competing theories exist that purport to explain

MDMA-induced neurotoxicity. One theory blames the deamination by MAO-B

of excessive dopamine taken up by the membrane-bound transporter

into the depleted serotonin terminals. This abnormal uptake follows

MDMA-induced reversal of the serotonin reuptake pump. In the absence

of MAO-B inhibition, deamination by MAO-B of excess dopamine taken up

into the serotonergic axon terminals is liable to generate a glut of toxic

free radicals. These highly reactive compounds cause membrane lipid

peroxidation and consequent fine terminal degeneration.

Selegiline prevents such serotonergic damage, in theory at any rate.

On the other hand, co-administering unselective selegiline dosages or

unselective irreversible MAOIs like tranylcypromine (Parnate) or

phenelzine (Nardil) with MDMA is potentially lethal.

Taken at MAO-B-selective dosages, selegiline is typically less effective

as a mood-brightener than other dopaminergics such as

amineptine (Survector) - though occasionally spectacular remission of

depressive symptoms may occur even with minimal MAO-A inhibition.

Taken at unselective dosages of 20mg a day or more, selegiline is

typically an effective, well-tolerated antidepressant. Selegiline at higher

dosages may also be useful for “atypical” depressive symptoms of overeating,

oversleeping, and hypersensitivity to rejection. An unselective dosage regimen

would normally call for an MAOI diet (no cheese, red wine, fava beans, salami, etc).

However, the gastrointestinal tract can be bypassed. Selegiline can be delivered

via a one-a-day transdermal patch. In December 2004, pharmaceutical firms

Bristol-Myers Squibb and Somerset Pharmaceuticals announced they had

entered into an agreement to distribute and commercialize EMSAM - the first

transdermal treatment for major depression. Better treatment of depression and

dysthymia is sorely needed. A February 2008 meta-analysis of

(published and unpublished) trials of several commonly prescribed “second generation”

antidepressants concluded that they were scarcely more effective than placebos.

Wrangling over labelling issues delayed EMSAM’s product launch. But in February

2006, the FDA granted EMSAM a product license for the treatment of major depressive

disorder in adults. EMSAM’s pharmacokinetic and pharmacodynamic properties promote the

inhibition of MAO-A and MAO-B in the CNS while avoiding significant inhibition of

intestinal and liver MAO-A enzyme. Three different strengths of EMSAM patch are

currently marketed: 20mg/20cm2, 30mg/30cm2, and 40mg/40cm2. The three patch sizes

deliver daily doses of selegiline averaging 6mg, 9mg and 12mg respectively. Use of the

lowest dosage EMSAM 6 mg/24 hour patch doesn’t call for dietary modification. Certainly

at the lower dosage range, MAO-A in the digestive tract is preserved at levels more than

adequate to break down tyramine, while MAO in the brain is inhibited at levels adequate to

induce an antidepressant effect. A restricted “MAOI diet” is prudently advised for the higher

dosage EMSAM 9 mg/24 hr patch and the 12 mg/24 hr patch to avoid any risk of hypertensive

crisis. But it’s worth noting that (as of 2008) no hypertensive crises following dietary

indiscretions have been reported even in users of the high strength patches. Other prescribing

indications for selegiline are in prospect. In November 2004, Yale University researchers

launched a study of selegiline for smokers who want to quit tobacco. Unlike selegiline,

the novel irreversible selective MAO-B-inhibitor rasagiline (Azilect) is not metabolised

to methamphetamine or amphetamine. These trace amines are unlikely to contribute to

selegiline’s neuroprotective action. Azilect has been licensed in the EC from mid-2005;

but labelling disputes with the FDA delayed the product launch of rasagiline/Azilect in

the USA until May 2006. Either way, by the standards of posterity we are all little better

than glorified glue-sniffers in the light of the chemicals we put into our bodies.

The impending Post-Darwinian Transition to an era of paradise-engineering has

dreadfully crude origins. But by today’s modest standards, at least, selegiline

is a

potentially life-enriching agent…"


is a

potentially life-enriching agent