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Details

Stereochemistry ABSOLUTE
Molecular Formula C12H13N
Molecular Weight 171.2383
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RASAGILINE

SMILES

C#CCN[C@@H]1CCC2=CC=CC=C12

InChI

InChIKey=RUOKEQAAGRXIBM-GFCCVEGCSA-N
InChI=1S/C12H13N/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12/h1,3-6,12-13H,7-9H2/t12-/m1/s1

HIDE SMILES / InChI

Molecular Formula C12H13N
Molecular Weight 171.2383
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Rasagiline (N-propargyl-1-(R)-aminoindan) is a selective, irreversible monoamine oxidase B (MAO B) inhibitor, which has been developed as an anti-Parkinson drug and was sold as a mesylate salt under brand name AZILECT. AZILECT is indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease (PD) as initial monotherapy and as adjunct therapy to levodopa. The effectiveness of AZILECT was demonstrated in patients with early Parkinson’s disease who were receiving AZILECT as monotherapy and who were not receiving any concomitant dopaminergic therapy. The effectiveness of AZILECT as adjunct therapy was demonstrated in patients with Parkinson’s disease who were treated with levodopa. PD is a progressive neurodegenerative, dopamine deficiency disorder. The main therapeutic strategies for PD treatment relies on dopamine precursors (levodopa), inhibition of dopamine metabolism (monoamine oxidase [MAO] B and catechol-O-methyl transferase inhibitors), and dopamine receptor agonists. In contrast to selegiline, rasagiline is not metabolized to potentially toxic amphetamine metabolites. The precise mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AZILECT

Approved Use

AZILECT (rasagiline tablets) is indicated for the treatment of Parkinson’s disease (PD). AZILECT, a monoamine oxidase (MAO)-B inhibitor (MAOI), is indicated for the treatment of Parkinson’s disease (1)

Launch Date

1.1477376E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
56.13 ng/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RASAGILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
53.53 ng × h/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RASAGILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.17 h
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RASAGILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2.5 mg single, transdermal
Dose: 2.5 mg
Route: transdermal
Route: single
Dose: 2.5 mg
Sources:
healthy, 22–25 years
n = 4
Health Status: healthy
Age Group: 22–25 years
Sex: M
Population Size: 4
Sources:
2 mg single, oral
Highest studied dose
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources:
healthy, 33 years
n = 16
Health Status: healthy
Age Group: 33 years
Sex: M+F
Population Size: 16
Sources:
2 mg 1 times / day steady, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
healthy, 33 years
n = 16
Health Status: healthy
Age Group: 33 years
Sex: M+F
Population Size: 16
Sources:
Other AEs: Ear discomfort, Musculoskeletal pain...
Other AEs:
Ear discomfort (1 patient)
Musculoskeletal pain (1 patient)
Sources:
4 mg 1 times / day steady, oral
Highest studied dose
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, 62.0 years
n = 14
Health Status: unhealthy
Condition: Early Parkinson’s Disease
Age Group: 62.0 years
Sex: M+F
Population Size: 14
Sources:
100 mg single, oral
Overdose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Population Size: 1
Sources:
Other AEs: Serotonin syndrome...
3 mg 1 times / day multiple, oral
Overdose
Dose: 3 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3 mg, 1 times / day
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Population Size: 1
Sources:
Other AEs: Hypertension, Orthostatic hypotension...
Other AEs:
Hypertension (1 patient)
Orthostatic hypotension (1 patient)
Sources:
1 mg 1 times / day steady, oral
Recommended
Dose: 1 mg, 1 times / day
Route: oral
Route: steady
Dose: 1 mg, 1 times / day
Sources:
unhealthy, adult
n = 149
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 149
Sources:
Disc. AE: Hallucinations...
AEs leading to
discontinuation/dose reduction:
Hallucinations
Sources:
AEs

AEs

AESignificanceDosePopulation
Ear discomfort 1 patient
2 mg 1 times / day steady, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
healthy, 33 years
n = 16
Health Status: healthy
Age Group: 33 years
Sex: M+F
Population Size: 16
Sources:
Musculoskeletal pain 1 patient
2 mg 1 times / day steady, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
healthy, 33 years
n = 16
Health Status: healthy
Age Group: 33 years
Sex: M+F
Population Size: 16
Sources:
Serotonin syndrome 1 patient
100 mg single, oral
Overdose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Population Size: 1
Sources:
Hypertension 1 patient
3 mg 1 times / day multiple, oral
Overdose
Dose: 3 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3 mg, 1 times / day
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Population Size: 1
Sources:
Orthostatic hypotension 1 patient
3 mg 1 times / day multiple, oral
Overdose
Dose: 3 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3 mg, 1 times / day
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Population Size: 1
Sources:
Hallucinations Disc. AE
1 mg 1 times / day steady, oral
Recommended
Dose: 1 mg, 1 times / day
Route: oral
Route: steady
Dose: 1 mg, 1 times / day
Sources:
unhealthy, adult
n = 149
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 149
Sources:
Overview

Overview

OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: ciprofloxacin increased rasagiline AUC by 83%
Page: 56, 57, 69
no
no
no (co-administration study)
Comment: hesperetin and narigenin enhanced the systemic exposure of rasagiline not through P-gp
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo.
2001 Jun
Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022.
2001 Jun
Neuroprotective effects of novel cholinesterase inhibitors derived from rasagiline as potential anti-Alzheimer drugs.
2001 Jun
Rasagiline. Teva Pharmaceutical.
2002 May
Anti-apoptotic function of propargylamine inhibitors of type-B monoamine oxidase.
2003
Anti-apoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor.
2003 May 8
The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline.
2003 Oct 15
A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.
2004 Apr
Neuroprotection in Parkinson's disease: an elusive goal.
2004 Jul
Rasagiline enhances L-DOPA-induced contralateral turning in the unilateral 6-hydroxydopamine-lesioned guinea-pig.
2004 Jul
Regulation of protein kinase C by the anti-Parkinson drug, MAO-B inhibitor, rasagiline and its derivatives, in vivo.
2004 Jun
Neuroprotective effect of rasagiline in a rodent model of Parkinson's disease.
2004 Jun
Clinical trials of neuroprotection for Parkinson's disease.
2004 Oct 12
Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson's disease.
2004 Oct 12
Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model.
2004 Sep
Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy.
2005
Novel pharmacological strategies for motor complications in Parkinson's disease.
2005 Apr
Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives.
2005 Apr
Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease.
2005 Aug
Neuroprotective effect of rasagiline, a monoamine oxidase-B inhibitor, on spontaneous cell degeneration in a rat model.
2005 Aug
Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases.
2005 Feb
[Rasagiline. A new monoamine oxidase b inhibitor for Parkinson treatment].
2005 Jul
In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET.
2005 Oct
Rasagiline in the pharmacotherapy of Parkinson's disease--a review.
2005 Oct
[Rasagiline in motor fluctuations].
2005 Sep
Neuroprotection by rasagiline: a new therapeutic approach to Parkinson's disease?
2005 Summer
Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's disease.
2006 Feb
Patents

Sample Use Guides

Monotherapy: the recommended AZILECT (RASAGILINE MESYLATE) dose for the treatment of Parkinson’s disease patients is 1 mg administered once daily. Adjunctive Therapy: the recommended initial dose is 0.5 mg administered once daily. If a sufficient clinical response is not achieved, the dose may be increased to 1 mg administered once daily. Change of levodopa dose in adjunct therapy: When AZILECT is used in combination with levodopa, a reduction of the levodopa dosage may be considered based upon individual response. During the controlled trials of AZILECT as adjunct therapy to levodopa, levodopa dosage was reduced in some patients. In clinical studies, dosage reduction of levodopa was allowed within the first 6 weeks if dopaminergic side effects, including dyskinesia and hallucinations, emerged.
Route of Administration: Oral
The present series of in vitro experiments using the rat hippocampal slice preparation deals with effects of rasagiline and its metabolite R-(-)-aminoindan on the pyramidal cell response after electric stimulation of the Schaffer Collaterals in comparison to selegiline, another MAO B inhibitor. During the first series, this response was attenuated in the presence of rasagiline and aminoindan-to a lesser degree of selegiline-in a concentration dependent manner (5-50 μM) after single stimuli as well as under theta burst stimulation (TBS). The presence of rasagiline and aminoindan, but rarely the presence of selegiline, prevented this break down. Following glutamate receptor mediated enhancements of neuronal transmission in a second series of experiments very clear differences could be observed in comparison to the action of selegiline: NMDA receptor, AMPA receptor as well as metabotropic glutamate receptor mediated increases of transmission were concentration dependently (0,3 - 2 μM) antagonized by rasagiline and aminoindan, but not by selegiline. On the opposite, only selegiline attenuated kainate receptor mediated increases of excitability. Thus, both monoamino oxidase (MAO) B inhibitors show attenuation of glutamatergic transmission in the hippocampus but interfere with different receptor mediated excitatory modulations at low concentrations.
Substance Class Chemical
Created
by admin
on Fri Dec 16 20:15:10 UTC 2022
Edited
by admin
on Fri Dec 16 20:15:10 UTC 2022
Record UNII
003N66TS6T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RASAGILINE
EMA EPAR   HSDB   INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
1H-INDEN-1-AMINE, 2,3-DIHYDRO-N-2-PROPYN-1-YL-, (1R)-
Systematic Name English
AGN-1135
Code English
NSC-759639
Code English
rasagiline [INN]
Common Name English
RASAGILINE [HSDB]
Common Name English
RASAGILINE [ORANGE BOOK]
Common Name English
(R)-(+)-RASAGILINE
Common Name English
RASAGILINE [VANDF]
Common Name English
TV-1030
Code English
(1R)-2,3-DIHYDRO-N-2-PROPYN-1-YL-1H-INDEN-1-AMINE
Systematic Name English
1H-INDEN-1-AMINE, 2,3-DIHYDRO-N-2-PROPYNYL-, (R)-
Systematic Name English
RASAGILINE [MI]
Common Name English
RASAGILINE [EMA EPAR]
Common Name English
1H-INDEN-1-AMINE, 2,3-DIHYDRO-N-2-PROPYNYL-, (1R)-
Systematic Name English
Rasagiline [WHO-DD]
Common Name English
RASAGILINE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C38149
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
WHO-ATC N04BD02
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
NDF-RT N0000175744
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
LIVERTOX NBK547919
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
NDF-RT N0000000184
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
NCI_THESAURUS C667
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
WHO-VATC QN04BD02
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
Code System Code Type Description
MERCK INDEX
M9504
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY Merck Index
EVMPD
SUB10261MIG
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
RXCUI
134748
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY RxNorm
CAS
136236-51-6
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
FDA UNII
003N66TS6T
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
EPA CompTox
DTXSID3041112
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
INN
7151
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
CHEBI
63620
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
WIKIPEDIA
RASAGILINE
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
MESH
C031967
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
PUBCHEM
3052776
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
DRUG BANK
DB01367
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
DAILYMED
003N66TS6T
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
IUPHAR
6641
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
HSDB
7699
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
LACTMED
Rasagiline
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
ChEMBL
CHEMBL887
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
NCI_THESAURUS
C66510
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
DRUG CENTRAL
3521
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
USAN
YY-124
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
NSC
759639
Created by admin on Fri Dec 16 20:15:10 UTC 2022 , Edited by admin on Fri Dec 16 20:15:10 UTC 2022
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
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SALT/SOLVATE -> PARENT
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TARGET -> INHIBITOR
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major metabolite, 1(R)-aminoindan, which is not an MAO inhibitor, has been therapeutically active in animal models relevant to Parkinson?s disease
MAJOR
PLASMA
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP1A2 being the major isoenzyme involved in rasagiline metabolism
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC