Desmethylselegiline

Clinical data
Other names	DMS;N-Desmethylselegiline; Norselegiline;L-Desmethyldeprenyl;L-DD;R-(–)-N-Desmethyldeprenyl;L-Nordeprenyl;N-Propargyl-L-amphetamine
Routes of administration	By mouth[1][2][3]
Drug class	Monoamine oxidase inhibitor;Catecholaminergic activity enhancer;Norepinephrine–dopamine releasing agent
Pharmacokinetic data
Metabolites	• Levoamphetamine[4][1][3]
Identifiers
IUPAC name 1-Phenyl-N-prop-2-ynylpropan-2-amine
CAS Number	18913-84-3 2588-96-7 (HCl)
PubChemCID	200718
ChemSpider	161558
ChEMBL	ChEMBL1276
CompTox Dashboard(EPA)	DTXSID001315731
Chemical and physical data
Formula	C12H15N
Molar mass	173.259 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=CC=CC=C1)NCC#C
InChI InChI=1S/C12H15N/c1-3-9-13-11(2)10-12-7-5-4-6-8-12/h1,4-8,11,13H,9-10H2,2H3 Key:UUFAJPMQSFXDFR-UHFFFAOYSA-N

Desmethylselegiline (DMS), also known asnorselegiline or asN-propargyl-L-amphetamine, is anactive metabolite ofselegiline, amedication used in the treatment ofParkinson's disease anddepression.^[4][1][2][3]

Like selegiline, DMS is amonoamine oxidase inhibitor (MAOI); specifically, it is aselective andirreversibleinhibitor ofmonoamine oxidase B (MAO-B).^[1][2][3] In addition, it is acatecholaminergic activity enhancer (CAE) similarly to selegiline.^[5][6] The drug also produceslevoamphetamine as anactive metabolite, which is anorepinephrine–dopamine releasing agent withsympathomimetic andpsychostimulant effects.^[1][7][8]

DMS has been studied much less extensively than selegiline and has not been developed or approved for medical use.^[9]

DMS is amonoamine oxidase inhibitor (MAOI), similarly toselegiline.^[1][2][3] It is specifically aselective andirreversibleinhibitor ofmonoamine oxidase B (MAO-B).^[1][2][3] The compound is also acatecholaminergic activity enhancer (CAE) like selegiline.^[5][6] Thepotency of DMS as a CAE appears to be similar to that of selegiline.^[5][6]

Aside from being anactive metabolite of selegiline, DMS itself has been studied clinically.^[1][10][3] A single 10 mgoral dose of DMS inhibitedplatelet MAO-B activity by 68 ± 16%, relative to 94 ± 9% with a single 10 mg dose of selegiline.^[1][2][3] Subsequently, platelet MAO-B activity returned to baseline after 2 weeks.^[1][2][3] Hence, although lesspotent than selegiline, DMS is also an effective MAO-B inhibitor.^[1][10][3]

DMS has been found to be 60-fold lesspotent than selegiline as an MAO-B inhibitorin vitro.^[1][2][11] However, it was only 3-fold less potent than selegiline orallyin vivo in rats with repeated administration.^{[1][2][9][11]} In other research, DMS was 6-fold less potent than selegiline in inhibition of platelet MAO-B activity.^[1][12]

Selegiline produceslevomethamphetamine andlevoamphetamine as active metabolites, whereas DMS produces only levoamphetamine as a metabolite.^[1] Unlike DMS and selegiline, levoamphetamine and levomethamphetamine are not active as MAO-B inhibitors at concentrations up to 100 μMin vitro.^[1][13] However, levoamphetamine is areleaser of norepinephrine and dopamine and hassympathomimetic andpsychostimulant effects.^{[7][8][note 1]} Similarly to selegiline, but unlike levoamphetamine and levomethamphetamine, DMS itself is not amonoamine releasing agent.^[14]

DMS showsneuroprotective,antioxidant, andantiapoptotic activity similarly to selegiline.^{[10][15][16][17]} DMS is more potent in some of these effects than selegiline.^[10][16][17] The neuroprotective and antioxidant properties of DMS and selegiline appear to be independent of MAO-B inhibition.^{[10][15][16][17]} Both selegiline and DMS have been found to bind to and inhibitglyceraldehyde-3-phosphate dehydrogenase (GAPDH), which may be involved in their neuroprotective effects.^[18][19]

Selegiline and DMS were compared in a clinical study in which 10 mg of each drug was administered orally.^[3] DMS showed 27-fold higherpeak levels and 33-fold higherarea-under-the-curve levels than selegiline in this study, suggesting that it has much greater oralbioavailability than selegiline.^[3]

Levoamphetamine is anactive metabolite of DMS.^[4][1][3] Conversely, in contrast to selegiline, which metabolizes into bothlevomethamphetamine and levoamphetamine, levomethamphetamine is not a metabolite of DMS.^[4][1][3]

Selegiline ismetabolized into DMS in theliver.^[20] With use of oral selegiline in humans, 86% of a dose isexcreted inurine, with 1.1% of this being DMS, 59.2% being levomethamphetamine, and 26.3% being levoamphetamine.^[20] Levoamphetamine is formed with selegiline from both DMS and levomethamphetamine.^[20][21] However, levoamphetamine is only a minor metabolite of levomethamphetamine (2–3%).^[21] As a metabolite of selegiline, DMS has anelimination half-life ranging from 2.6 to 11 hours.^[1] The half-lives of both selegiline and DMS increase with continuous use of selegiline.^[1]

Prodrugs of DMS have beensynthesized and studied.^[22][23]

• Antiparkinsonian agents
• Drugs with unknown mechanisms of action
• Enantiopure drugs
• Human drug metabolites
• Monoamine oxidase inhibitors
• Monoaminergic activity enhancers
• Neuroprotective agents
• Norepinephrine-dopamine releasing agents
• Prodrugs
• Propargyl compounds
• Stimulants
• Substituted amphetamines
• TAAR1 agonists
• Selegiline

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