SELEGILINE

First approved in 1989

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H17N
Molecular Weight	187.2808
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](CC1=CC=CC=C1)N(C)CC#C

InChI

InChIKey=MEZLKOACVSPNER-GFCCVEGCSA-N

InChI=1S/C13H17N/c1-4-10-14(3)12(2)11-13-8-6-5-7-9-13/h1,5-9,12H,10-11H2,2-3H3/t12-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C13H17N
Molecular Weight	187.2808
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/dosage/selegiline.html
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01037 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021708s000_021336s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18237459 | https://www.ncbi.nlm.nih.gov/pubmed/28108387

Selegiline, also known as L-deprenyl, is a substituted phenethylamine, a selective, irreversible inhibitor of Type B monoamine oxidase. Selegiline is available in pill form under many brand names (Eldepryl, Carbex, Atapryl) and is used to reduce symptoms in early-stage Parkinson's disease. Selegiline delays the time point when the L-DOPA (levodopa) treatment becomes necessary from about 11 months to about 18 months after diagnosis, which is beneficial despite not being definitive evidence of neuroprotection. The rationale for adding selegiline to levodopa is to decrease the required dose of levodopa and thus reduce the motor complications of levodopa therapy. Selegiline is also delivered via a transdermal patch (brand name, Emsam) and in this form, Selegiline is used as a treatment for the major depressive disorder. Selegiline (brand name Anipryl) is also used (at extremely high dosages relative to humans) in veterinary medicine to treat the symptoms of Cushing's disease and cognitive dysfunction (Canine Cognitive Dysfunction) in dogs. Side effects of the pill form include, in decreasing order of frequency, nausea, hallucinations, confusion, depression, loss of balance, insomnia, increased involuntary movements, agitation, arrhythmia, slow heart rate, delusions, hypertension, new or increased angina pectoris, and syncope. The main side effects of the patch form for depression included application site reactions, insomnia, diarrhea, and sore throat.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26337020	Inhibitor 8297		9.0 nM [IC50]
Monoamine oxidase A 49 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26278660	Inhibitor 8297		47.9 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.drugs.com/dosage/selegiline.html	Primary	Approved 8429	EMSAM Approved Use Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). Launch Date 2006
Major depressive disorder 173 Sources: https://www.drugs.com/dosage/selegiline.html	Primary	Approved 8429	EMSAM Approved Use Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). Launch Date 2006
Bipolar depression 9 Sources: https://www.drugs.com/dosage/selegiline.html	Primary	Approved 8429	EMSAM Approved Use Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). Launch Date 2006
Cocaine-related disorders 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00032929	Primary	Phase III 656	EMSAM Approved Use Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). Launch Date 2006
Cognitive disorders 8 Sources: https://clinicaltrials.gov/ct2/show/NCT00002154	Primary	Phase II 1132	EMSAM Approved Use Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). Launch Date 2006

C_max

Value	Dose	Co-administered	Analyte	Population
8.9 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10215747	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SELEGILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
11 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10215747	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SELEGILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021479s005lbl.pdf	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:		SELEGILINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10215747	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SELEGILINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
15% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021479s005lbl.pdf	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:		SELEGILINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 mg 1 times / day multiple, transdermal Highest studied dose Dose: 12 mg, 1 times / day Route: transdermal Route: multiple Dose: 12 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/	unhealthy, adult n = 116 Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sex: M+F Population Size: 116 Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/	Other AEs: Headache, Infection... Other AEs: Headache (16%) Infection (15%) Back pain (6%) Diarrhea (11%) Nausea (7%) Insomnia (32%) Dry mouth (13%) Dizziness (14%) Nervousness (10%) Somnolence (5%) Anxiety (5%) Abnormal dreams (5%) Pharyngitis (7%) Application site reaction (44%) Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/
12 mg 1 times / day multiple, transdermal (max) Recommended Dose: 12 mg, 1 times / day Route: transdermal Route: multiple Dose: 12 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/	unhealthy, adult n = 817 Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sex: M+F Population Size: 817 Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/	Other AEs: Headache, Infection... Other AEs: Headache (18%) Infection (9%) Back pain (3%) Diarrhea (9%) Nausea (5%) Insomnia (12%) Dry mouth (8%) Dizziness (5%) Nervousness (4%) Somnolence (3%) Anxiety (3%) Abnormal dreams (2%) Pharyngitis (3%) Application site reaction (24%) Sources: https://pubmed.ncbi.nlm.nih.gov/17568687/
2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Co-administed with:: levodopa Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021479s003s004lbl.pdf	unhealthy, adult n = 194 Health Status: unhealthy Condition: Parkinson’s disease Age Group: adult Sex: M+F Population Size: 194 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021479s003s004lbl.pdf	Other AEs: Back pain, Chest pain... Other AEs: Back pain (5%) Chest pain (2%) Pain (8%) Hypertension (3%) Constipation (4%) Diarrhea (2%) Dysphagia (2%) Dyspepsia (5%) Flatulence (2%) Nausea (11%) Stomatitis (5%) Tooth disorder (2%) Vomiting (3%) Ecchymosis (2%) Hypokalemia (2%) Leg cramps (3%) Myalgia (3%) Ataxia (3%) Depression (2%) Dizziness (11%) Dry mouth (4%) Dyskinesia (6%) Hallucinations (4%) Headache (7%) Insomnia (7%) Somnolence (3%) Tremor (3%) Dyspnea (3%) Pharyngitis (4%) Rhinitis (7%) Rash (4%) Skin disorder (6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021479s003s004lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 CYP2B6 810 UGT2B10 25	P-gp 1537 CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
UGT2B10 27	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26669329/	yes [IC50 67.2 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18065502/	yes [Ki 15.6 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25656918/	yes [Ki 22 uM]

Drug as victim

Target	Modality	Activity
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/ \| https://pubmed.ncbi.nlm.nih.gov/12920164/ \| https://pubmed.ncbi.nlm.nih.gov/17495414/ \| https://pubmed.ncbi.nlm.nih.gov/15618670/	major
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/ \| https://pubmed.ncbi.nlm.nih.gov/12920164/ \| https://pubmed.ncbi.nlm.nih.gov/10862503/ \| https://pubmed.ncbi.nlm.nih.gov/15618670/	major
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/ \| https://pubmed.ncbi.nlm.nih.gov/12920164/ \| https://pubmed.ncbi.nlm.nih.gov/10862503/ \| https://pubmed.ncbi.nlm.nih.gov/15618670/	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/ \| https://pubmed.ncbi.nlm.nih.gov/10862503/ \| https://pubmed.ncbi.nlm.nih.gov/17495414/ \| https://pubmed.ncbi.nlm.nih.gov/15618670/	minor
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12438524/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11602525/ \| https://pubmed.ncbi.nlm.nih.gov/12920164/	yes

PubMed

Title	Date	PubMed
Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.	1999 Mar	10091617
Antioxidant activity of the monoamine oxidase B inhibitor lazabemide.	2000 Sep 1	10927030
[The effect of selegiline and vitamin E in the treatment of ALS: an open randomized clinical trials].	2001	11732275
Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment.	2001	11599635
Long-term persistence of symptomatic effect of selegiline in Parkinson's disease. A two-months placebo-controlled withdrawal study.	2001	11314774
Do antioxidant strategies work against aging and age-associated disorders? Propargylamines: a possible antioxidant strategy.	2001 Apr	11795516
Selegiline pharmacokinetics are unaffected by the CYP3A4 inhibitor itraconazole.	2001 Apr	11372588
Selective inhibition of MAO-B through chronic low-dose (R)-deprenyl treatment in C57BL/6 mice has no effect on basal neostriatal dopamine levels.	2001 Apr	11259132
Inhibition of rat liver microsomal CYP1A2 and CYP2B1 activity by N-(2-heptyl)-N-methyl-propargylamine and by N-(2-heptyl)-propargylamine.	2001 Aug	11454735
Zonisamide has beneficial effects on Parkinson's disease patients.	2001 Dec	11755227
Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain.	2001 Fall	11607046
The economic consequences of a drug-drug interaction.	2001 Feb	11199940
Selegiline completely restores choline acetyltransferase activity deficits in simian immunodeficiency infection.	2001 Jan 5	11137877
Different sensitivity of mitochondrial and cytosolic monoamine oxidases to in vivo but not in vitro inhibition by specific irreversible inhibitors.	2001 Jan-Feb	11208486
Paroxysmal hypertensive crises induced by selegiline in a patient with Parkinson's disease.	2001 Jun	11499649
Inhibition of MAO-A activity enhances behavioural activity of rats assessed using water maze and open arena tasks.	2001 Jun	11453370
The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor syndrome.	2001 Jun	11442353
[A behavioral and neurochemical study on the mechanism of the anxiolytic effect of monoamine oxidase inhibitors].	2001 May	11481866
Semicarbazide-sensitive amine oxidase substrates stimulate glucose transport and inhibit lipolysis in human adipocytes.	2001 May	11303044
The effects of oral selegiline hydrochloride on learning and training in the dog: a psychobiological interpretation.	2001 Nov	11642657
CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes.	2001 Nov	11602525
Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial.	2001 Nov 13	11706112
(-)-D-Deprenyl attenuates apoptosis in experimental brain ischaemia.	2001 Nov 2	11711036
Chronic daily administration of selegiline and EGb 761 increases brain's resistance to ischemia in mice.	2001 Nov 2	11640903
Incorporation of selegiline metabolites into hair after oral selegiline intake.	2001 Oct	11599606
Drug-induced psychotic symptoms in Parkinson's disease. Problems, management and dilemma.	2001 Sep	11697685
Effect of repeated treatment with high doses of selegiline on behaviour, striatal dopaminergic transmission and tyrosine hydroxylase mRNA levels.	2002 Jan	11862330
The influence of metabolism on the MAO-B inhibitory potency of selegiline.	2002 Jan	11860347
Neuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells.	2002 Jan 11	11779573
Deprenyl protects from MPTP-induced Parkinson-like syndrome and glutathione oxidation in rat striatum.	2002 Jan 25	11788154

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Parkinson's Disease: Recommended dose: 5 mg orally twice a day, Maximum dose: 10 mg orally per day Usual Adult Dose for Depression: Initial dose: Apply one 6 mg/24 hours transdermal patch to intact skin once every 24 hours, Maintenance dose: One 6 mg/24 hours to 12 mg/24 hours transdermal patch applied to the skin once a day, Maximum dose: 12 mg/24 hours transdermal patch applied to the skin once a day

Route of Administration: Other

In Vitro Use Guide

BEAS-2B cells were seeded in 6 cm dishes. Cells were pretreated with 100 nM selegiline for 30 min before further exposed to 2% CSM for 24 h. Total protein was extracted. Monoamine Oxidase Activity Fluorometric Assay Kit (BioVision Inc., Milpitas, CA, USA), Superoxide Dismutase (SOD) Detection kit (Nanjing Jiancheng Bioenginering Inst., China), Amplex Red Catalase Assay kit (Molecular Probes, Inc., Eugene, OR, USA) and Oxidative Glutathi-one (GSSG) Detection Kit (Nanjing Jiancheng Bioenginering Y. Cui et al. / Toxicology Letters 268 (2017) 44–50 45Inst., China) were used for MAO, SOD and CAT activities and GSH/GSSG ratio measurement, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:51:21 GMT 2023` Edited by `admin` on `Sat Dec 16 16:51:21 GMT 2023`
Record UNII	2K1V7GP655
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SELEGILINE

Official Name

English

SELEGILINE [ORANGE BOOK]

Common Name

English

Selegiline [WHO-DD]

Common Name

English

SELEGILINE [VANDF]

Common Name

English

EMSAM

Brand Name

English

SELEGILINE [MI]

Common Name

English

selegiline [INN]

Common Name

English

BENZENEETHANAMINE, N,.ALPHA.-METHYL-N-2-PROPYNYL-, (.ALPHA.R)-

Common Name

English

(-)-(N)-METHYL-N-((1R)-1-METHYL-2-PHENYLETHYL)PROP-2-YN-1-AMINE

Common Name

English

L-SELEGILINE

Common Name

English

SELEGILINE [USAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175761