L-deprenyl (Selegiline, Eldepryl, Emsam, Zelapar)

Indications

• treatment of the symptoms of Parkinson's disease
• adjunctive treatment to carbidopa/L-dopa
• symptomatic treatment of Alzheimer's disease

Contraindications

• coadministration of dextromethorphan, meperidine, methadone, propoxyphene

pregnancy category = c

safety in lactation = ?

Dosage

• 5 mg PO BID (breakfast & lunch dosing)
• after 2-3 days of treatment, try to decreased L-dopa/ carbidopa by 30-30%
• giving the dose in the evening increases insomnia & nightmares
• doses > 10 mg/day decreases MAO-B selectivity
• transdermal patch: 1 patch QD
  • apply to dry, intact skin on upper torso, upper thigh, or outer surface of upper arm
• Zelapar 1.25-2.5 mg PO QD

Tabs: 5 mg.

Transdermal patch: (Emsam) 6, 9, 12 mg (box of 30)

Zelapar: 1.25 mg, 2.5 mg

Pharmacokinetics

• about 75% of oral dose is absorbed from the GI tract
• metabolized by the liver
• metabolized to 2 amphetamine derivatives that enhance release & decrease re-uptake of dopamine
• excreted in the urine

elimination via liver

elimination via kidney

Adverse effects

• common (> 10%)
  • mood changes, dyskinesias, dizziness, dry mouth, nausea/vomiting, insomnia, abdominal pain
• less common (1-10%)
  • orthostatic hypotension, arrhythmias, hypertension, hallucinations, confusion, depression, insomnia, agitation, increased involuntary movements, bradykinesia, bruxism, muscle twitches
• other
  • nightmares
  • ataxia
  • tachycardia

• drug adverse effects of MAO inhibitors
• drug adverse effects of antidepressants
• drug adverse effects of psychotropic agents

Drug interactions

• meperidine: mechanism unknown; fatal reactions have occurred
• use in combination with:
  • other antidepressants
    • selective serotonin re-uptake inhibitors (SSRI)
    • tricyclic antidepressants (TCA)
  • buspirone, cyclobenzaprine, dextromethorphan, meperidine, methadone, propoxyphene tramadol, St. John's wort can cause serotonin syndrome
• amphetamines, pseudoephedrine, phenylephrine in combination may result in excessive sympathetic stimulation... hypertension
• carbamazepine, oxcarbazepine in combination can increase deprenyl levels

• drug interaction(s) of benzodiazepines with antidepressants
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with MAO inhibitors
• drug interaction(s) of NSAIDs with antidepressants
• drug interaction(s) of MAO inhibitor with caffeine

Mechanism of action

• selective MAO-B inhibitor
  • MAO-B accounts for 70% of MAO in brain
• in contrast to nonspecific MAO inhibitors, deprenyl does NOT cause profound & potentially lethal potentiation of catechol- amines when administered concurrently with indirect sympatho- mimetic amines
• inhibits CNS degradation of dopamine
• potentiates the effects of L-dopa
• metabolized to 2 amphetamine derivatives that enhance release & decrease re-uptake of dopamine
• it has been suggested that MAO-B inhibitors may slow the progression of Parkinson's disease; however, this issue is controversial
• symptomatic improvement in Alzheimer's disease
  • does not alter the course of the disease

More general terms

• monoamine oxidase [MAO] inhibitor
• aromatic compound
• amine
• alkyne
• pharmacologic agents for treatment of Parkinson's disease

Additional terms

• Alzheimer's disease (ADD)
• monoamine oxidase [MAO]-B
• Parkinson's disease (paralysis agitans, PD)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5195
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5288103
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=26758
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=92913
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=199604
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=26757