RASAGILINE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C12H13N.C4H6O6
Molecular Weight	492.5635
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.C#CCN[C@@H]1CCC2=CC=CC=C12.C#CCN[C@@H]3CCC4=CC=CC=C34

InChI

InChIKey=YGKHOZXCTLKSLJ-KHAGDFGNSA-N

InChI=1S/2C12H13N.C4H6O6/c2*1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;5-1(3(7)8)2(6)4(9)10/h2*1,3-6,12-13H,7-9H2;1-2,5-6H,(H,7,8)(H,9,10)/t2*12-;1-,2-/m111/s1

HIDE SMILES / InChI

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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	( + )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021641lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18488080

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.

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/19673610	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Idiopathic Parkinson's disease 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021641lbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Co-administered	Analyte	Population
56.13 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15628826	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

Value	Dose	Co-administered	Analyte	Population
53.53 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15628826	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15628826	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

Dose	Population	Adverse events
2.5 mg single, transdermal Dose: 2.5 mg Route: transdermal Route: single Dose: 2.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/29159774	healthy, 22–25 years n = 4 Health Status: healthy Age Group: 22–25 years Sex: M Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29159774	Sources: https://pubmed.ncbi.nlm.nih.gov/29159774
2 mg single, oral Highest studied dose Dose: 2 mg Route: oral Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30218626	healthy, 33 years n = 16 Health Status: healthy Age Group: 33 years Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/30218626	Sources: https://pubmed.ncbi.nlm.nih.gov/30218626
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: https://pubmed.ncbi.nlm.nih.gov/30218626	healthy, 33 years n = 16 Health Status: healthy Age Group: 33 years Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/30218626	Other AEs: Ear discomfort, Musculoskeletal pain... Other AEs: Ear discomfort (1 patient) Musculoskeletal pain (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30218626
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: https://pubmed.ncbi.nlm.nih.gov/15300656	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: https://pubmed.ncbi.nlm.nih.gov/15300656	Sources: https://pubmed.ncbi.nlm.nih.gov/15300656
100 mg single, oral Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unknown, adult n = 1 Health Status: unknown Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	Other AEs: Serotonin syndrome... Other AEs: Serotonin syndrome (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unknown, adult n = 1 Health Status: unknown Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	Other AEs: Hypertension, Orthostatic hypotension... Other AEs: Hypertension (1 patient) Orthostatic hypotension (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unhealthy, adult n = 149 Health Status: unhealthy Condition: Parkinson’s disease Age Group: adult Population Size: 149 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	Disc. AE: Hallucinations... AEs leading to discontinuation/dose reduction: Hallucinations Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/30218626	healthy, 33 years n = 16 Health Status: healthy Age Group: 33 years Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/30218626
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: https://pubmed.ncbi.nlm.nih.gov/30218626	healthy, 33 years n = 16 Health Status: healthy Age Group: 33 years Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/30218626
Serotonin syndrome	1 patient	100 mg single, oral Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unknown, adult n = 1 Health Status: unknown Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unknown, adult n = 1 Health Status: unknown Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unknown, adult n = 1 Health Status: unknown Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf	unhealthy, adult n = 149 Health Status: unhealthy Condition: Parkinson’s disease Age Group: adult Population Size: 149 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201971Orig1s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2C19 1463 CYP2E1 876 CYP4A 19	CYP1A2 1032 P-gp 1527 CYP2A6 523

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no
CYP4A 33	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 57, 95	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 56, 57, 69	major	yes (co-administration study) Comment: ciprofloxacin increased rasagiline AUC by 83% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 56, 57, 69
CYP2A6 523	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_ClinPharmR.pdf Page: 97.0	no
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/26530401/	no	no (co-administration study) Comment: hesperetin and narigenin enhanced the systemic exposure of rasagiline not through P-gp Sources: https://pubmed.ncbi.nlm.nih.gov/26530401/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021641s000_Azilect_PharmR.pdf Page: 265.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63620	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63620
ChemicalBook	CB2459598	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2459598
MolPort	MolPort-003-850-132	https://www.molport.com/shop/molecule-link/MolPort-003-850-132
ZINC	ZINC000019875504	http://zinc15.docking.org/substances/ZINC000019875504
eMolecules	2727012	https://www.emolecules.com/cgi-bin/more?vid=2727012

PubMed

Title	Date	PubMed
Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.	2001	11716151
Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.	2003 Nov 17	14612913
Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease?	2004 Jan	14696044
Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor.	2004 Oct	15628826
Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson's disease.	2004 Oct 12	15477581
Alternatives to levodopa in the initial treatment of early Parkinson's disease.	2005	16156677
Novel neuroprotective mechanism of action of rasagiline is associated with its propargyl moiety: interaction of Bcl-2 family members with PKC pathway.	2005 Aug	16179541
A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.	2005 Feb	15710852
Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition.	2005 Jan 1-15	15573406
Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.	2005 Mar 12-18	15766996
Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.	2005 May	15818599
Rationale for considering that propargylamines might be neuroprotective in Parkinson's disease.	2006 May 23	16717254
Safety of rasagiline in elderly patients with Parkinson disease.	2006 May 9	16682679

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Thu Jul 06 01:32:31 UTC 2023` Edited by `admin` on `Thu Jul 06 01:32:31 UTC 2023`
Record UNII	B9A329CN07
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RASAGILINE TARTRATE

Common Name

English

1-H-INDEN-1-AMINE, 2,3-DIHYDRO-N-2-PROPYN-1-YL-, 1(R)-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (2:1)

Common Name

English

Rasagiline tartrate [WHO-DD]

Common Name

English

RASAGILINE HEMITARTRATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C667