selegiline

selegiline
IUPAC name	(R)-N-Methyl-N-(1-phenylpropan-2-yl)prop-2-yn-1-amine
Width	200
Tradename	Eldepryl, Emsam, others
Drugs.com	Monograph
MedlinePlus	a697046
Licence US	Selegiline
Pregnancy AU	B3
Routes of administration	By mouth, transdermal
CAS number	14611-51-9
PubChem	26757
DrugBank	DB01037
ChemSpiderID	24928
UNII	2K1V7GP655
ChEBI	8988
ChEMBL	521
ATC prefix	N04
ATC suffix	BD02
Synonyms	L-Deprenyl

selegiline. It is a medication primarily used in the treatment of Parkinson's disease and major depressive disorder. As a selective and irreversible monoamine oxidase inhibitor, it increases levels of certain chemicals in the brain, such as dopamine and phenethylamine. The drug is marketed under various brand names including Eldepryl and Emsam, and has a distinct history rooted in neuropharmacology research.

Medical uses

selegiline is indicated for the management of Parkinson's disease, often as an adjunct therapy to levodopa and carbidopa. It is also approved for the treatment of major depressive disorder when administered via a transdermal patch system. Clinical studies, such as those published in the Journal of the American Medical Association, have demonstrated its efficacy in delaying the need for levodopa in early disease. Its use in disorders like attention deficit hyperactivity disorder has been explored, though it is not a primary treatment. The Food and Drug Administration has granted approval for its various formulations based on trials conducted at institutions like the National Institutes of Health.

Adverse effects

Common adverse effects include insomnia, nausea, dizziness, and dry mouth. At higher doses, especially without dietary modification, there is a risk of the hypertensive crisis associated with tyramine ingestion, known as the "cheese reaction." Serious but rare side effects can involve serotonin syndrome, particularly when combined with other serotonergic agents like fluoxetine. Post-marketing surveillance by agencies such as the European Medicines Agency continues to monitor its safety profile. Reports in the British Medical Journal have documented cases of orthostatic hypotension and confusion in elderly patients.

Pharmacology

selegiline acts as an irreversible inhibitor of the enzyme monoamine oxidase B, with much greater affinity for this isoform over monoamine oxidase A at low doses. This inhibition leads to increased levels of dopamine and phenethylamine in the central nervous system. Its metabolites include L-amphetamine and L-methamphetamine, which may contribute to mild stimulant effects. The drug's action is primarily within the brain, affecting pathways like the nigrostriatal pathway. Research from the Karolinska Institute has detailed its neuroprotective properties in models of neurodegeneration.

Chemistry

selegiline is a synthetic compound belonging to the class of propynylamine derivatives. Its chemical name is (R)-N-Methyl-N-(1-phenylpropan-2-yl)prop-2-yn-1-amine, and it is the enantiomer of the R configuration at its chiral center. The molecule features a phenyl ring and a propargyl group, the latter being critical for its irreversible inhibition of monoamine oxidase. It is a lipophilic liquid at room temperature and is formulated as a hydrochloride salt for pharmaceutical use. The compound's structure was first elucidated in laboratories associated with Chinoin, a Hungarian pharmaceutical company.

History

selegiline was first synthesized in the 1960s by Joseph Knoll, a Hungarian pharmacologist working at the Semmelweis University. It was developed as a derivative of phenethylamine with the intent of creating a selective monoamine oxidase inhibitor. The drug gained prominence following clinical trials in the 1970s and 1980s, notably those conducted by Merton Sandler at the Royal Postgraduate Medical School. Its approval for Parkinson's disease in the United States came in 1989, followed by approval for depression in 2006. The development of the transdermal patch was a significant advancement led by Somerset Pharmaceuticals.

Society and culture

selegiline is available under several brand names globally, including Eldepryl, Zelapar, and Emsam. It is on the World Health Organization's List of Essential Medicines. The drug has been referenced in popular media, including an episode of the television series House. Its cost and availability are subjects of healthcare policy discussions in systems like the National Health Service. Patent disputes have involved companies such as Mylan and Bristol-Myers Squibb. Furthermore, its potential for cognitive enhancement has been a topic in publications like New Scientist.

Category:Drugs