Selegiline

Structural formula
General
Non-proprietary name	Selegiline
other names	( R ) - N -Methyl- N - [1-methyl-2-phenylethyl] prop-2- yn -1-amine ( IUPAC ); L -deprenyl; Selegilinum ( Latin );
Molecular formula	C 13 H 17 N
Brief description	White to almost white, crystalline powder ( hydrochloride )
External identifiers / databases
EC number	604-507-3
ECHA InfoCard	100.109.269
PubChem	26757
DrugBank	DB01037
Wikidata	Q47495783
Drug information
ATC code	N04 BD01
Drug class	MAO-B inhibitors , anti-Parkinson drugs
Mechanism of action	Enzyme inhibition of monoamine oxidase – B
properties
Molar mass	187.28 g · mol -1
Physical state	firmly
Melting point	141–142 ° C ( hydrochloride )
boiling point	92-93 ° C (1.07 k Pa)
solubility	Easily soluble in water , chloroform and methanol , poorly soluble in acetone ( hydrochloride )
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Hydrochloride	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	81 mg kg −1 ( LD 50 , rat , iv , hydrochloride) ; 280 mg kg −1 ( LD 50 , rat , sc , hydrochloride) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Selegiline is a drug that is used for the symptomatic treatment of Parkinson's disease . This substance mediates its effect via an irreversible inhibition of the enzyme monoamine oxidase B ( MAO-B inhibitor ) and thus an inhibition of dopamine breakdown in the brain . Selegiline is sold in Germany under the brand names Movergan, Antiparkin and Xilopar as well as under a generic name. Selegiline is subject to medical prescription .

Selegiline was discovered by József Knoll .

Stereoisomerism

N -Methyl- N - (1-methyl-2-phenylethyl) prop-2- yn -1-amine has a stereocenter and is therefore a chiral compound of which there are two isomers . Selegiline is the ( R ) form (also L -elegiline or (-) - selegiline). The hydrochloride is also used pharmaceutically .

The racemate, a 1: 1 mixture of ( R ) - and ( S ) -form, is also known as deprenyl. The hydrochloride is also used here.

(+) - or ( S ) -selegiline, on the other hand, has no meaning.

pharmacology

application areas

In combination with levodopa , selegiline is used for the symptomatic treatment of Parkinson's disease . Selegiline is primarily used in patients with a fluctuating clinical picture (dyskinesia, end-of-dose fluctuations, on-off phenomena). In addition, selegiline is approved as a monotherapy for the treatment of early stages of Parkinson's disease.

In the USA, selegiline is also used to treat depression , but there is no approval for this application in Germany. A discussed possible effectiveness of selegiline for improving the symptoms of Alzheimer's disease was judged negatively after a meta-analysis of patient data.

In veterinary medicine, selegiline is used to treat behavioral disorders of emotional or geriatric origin in dogs.

Mechanism of action

As an MAO-B inhibitor, selegiline is an inhibitor of the enzyme monoamine oxidase B. The inhibition of this enzyme leads to an inhibition of the breakdown of dopamine and thus to an increase in the pathologically decreased dopamine concentration in the brain.

Side effects

The following side effects in particular have been described with the use of selegiline: dry mouth , loss of appetite, dizziness , sleep disturbances , confusion , anxiety , hallucinations , transaminase increase , orthostatic hypotension and cardiac arrhythmias .

Interactions

The breakdown of drugs, which takes place via the monoamine oxidases, can be slowed down by selegiline. On the other hand, no undesirable effects are to be expected from the combined intake of selegiline (max. 10 mg / day) with foods containing tyramine , since the MAO-B selectivity means that monoamine oxidase A is still available for the breakdown of tyramine.

Selegiline can increase the effects and side effects of sympathomimetics , psychostimulants , nasal drops , antihypotonic drugs , antihypertensive drugs , sedatives, and ethanol .

Taking selegiline and antidepressants (especially SSRIs such as fluoxetine ) at the same time can lead to serious reactions such as: B. Flush , hyperthermia , seizures , cardiovascular disorders, psychological disorders (confusion, hallucinations) up to coma.

Selegiline also increases the MAO-inhibiting side effects of linezolid .

Manufacturing

A multi-step synthesis for selegiline, starting from ( RS ) - methamphetamine , is described in the literature.

Trade names

Monopreparations

Amboneural (A), Antiparkin (D), Cognitiv (A), Jumex (A), Jutagilin (D), Movergan (D), Selepark (D), Xilopar (D, A), numerous generics (D, A)

Veterinary medicine

Selgian

Web links

Commons : Selegiline - Collection of images, videos and audio files

Individual evidence

↑ ^a ^b ^c European Pharmacopoeia Commission (Ed.): EUROPÄISCHE PHARMACOPÖE 5th EDITION . tape 5.0 - 5.7 , 2006.
↑ ^a ^b ^c Entry on selegiline. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.
↑ ^a ^b Data sheet R - (-) - Deprenyl hydrochloride from Sigma-Aldrich , accessed on January 4, 2012 ( PDF ).
↑ External identifiers of or database links to (-) - selegiline hydrochloride : CAS number: 14611-52-0, EC number: 604-508-9, ECHA InfoCard: 100.109.608 , PubChem : 26758 , ChemSpider : 24931 , DrugBank : DBSALT000260 , Wikidata : Q27108267 .
↑ External identifiers or database links for Deprenyl : CAS number: 2323-36-6, PubChem : 5195 , ChemSpider : 5007 , Wikidata : Q402633 .
↑ External identifiers or database links for deprenyl hydrochloride : CAS number: 2079-54-1, EC number: 643-087-6, ECHA InfoCard: 100.171.140 , PubChem : 92913 , ChemSpider : 83874 , Wikidata : Q27263610 .
↑ External identifiers of or database links to (+) - selegiline : CAS number: 4528-51-2, PubChem : 199605 , ChemSpider : 172774 , Wikidata : Q5203251 .
↑ J. Birks, L. Flicker: Selegiline for Alzheimer's disease. In: Cochrane Database Syst. Rev. 2003, S. CD000442, PMID 12535396 .
↑ Entry on selegiline at Vetpharm, accessed on November 7, 2019.
↑ Pharmama: Tyramine and MAOIs
^ Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dietmar Reichert: Pharmaceutical Substances. 4th edition. Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 .

[Ph._Eur._5-1] European Pharmacopoeia Commission (Ed.): EUROPÄISCHE PHARMACOPÖE 5th EDITION . tape 5.0 - 5.7 , 2006.

[RÖMPP_Online-2] Entry on selegiline. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.

[sigma-3] Data sheet R - (-) - Deprenyl hydrochloride from Sigma-Aldrich , accessed on January 4, 2012 ( PDF ).

[4] External identifiers of or database links to (-) - selegiline hydrochloride : CAS number: 14611-52-0, EC number: 604-508-9, ECHA InfoCard: 100.109.608 , PubChem : 26758 , ChemSpider : 24931 , DrugBank : DBSALT000260 , Wikidata : Q27108267 .

[5] External identifiers or database links for Deprenyl : CAS number: 2323-36-6, PubChem : 5195 , ChemSpider : 5007 , Wikidata : Q402633 .

[6] External identifiers or database links for deprenyl hydrochloride : CAS number: 2079-54-1, EC number: 643-087-6, ECHA InfoCard: 100.171.140 , PubChem : 92913 , ChemSpider : 83874 , Wikidata : Q27263610 .

[7] External identifiers of or database links to (+) - selegiline : CAS number: 4528-51-2, PubChem : 199605 , ChemSpider : 172774 , Wikidata : Q5203251 .

[8] J. Birks, L. Flicker: Selegiline for Alzheimer's disease. In: Cochrane Database Syst. Rev. 2003, S. CD000442, PMID 12535396 .

[9] Entry on selegiline at Vetpharm, accessed on November 7, 2019.

[10] Pharmama: Tyramine and MAOIs

[A._Kleemann-11] Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dietmar Reichert: Pharmaceutical Substances. 4th edition. Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 .