Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C12H13N.CH4O3S |
| Molecular Weight | 267.344 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.C#CCN[C@@H]1CCC2=CC=CC=C12
InChI
InChIKey=JDBJJCWRXSVHOQ-UTONKHPSSA-N
InChI=1S/C12H13N.CH4O3S/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;1-5(2,3)4/h1,3-6,12-13H,7-9H2;1H3,(H,2,3,4)/t12-;/m1./s1
| 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 | ( + ) |
| Molecular Formula | CH4O3S |
| Molecular Weight | 96.106 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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 |
|---|---|---|---|
Target ID: CHEMBL2039 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | AZILECT Approved UseAZILECT (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 Date2006 |
Cmax
| 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 |
T1/2
| 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: |
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 |
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) Sources: Musculoskeletal pain (1 patient) |
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... Other AEs: Serotonin syndrome (1 patient) Sources: |
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) Sources: Orthostatic hypotension (1 patient) |
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
| 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: |
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
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical 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
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. | 2001 Aug |
|
| Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. | 2001 Jan |
|
| The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. | 2001 Jun |
|
| Novel neuroprotective anti-Alzheimer drugs with anti-depressant activity derived from the anti-Parkinson drug, rasagiline. | 2002 Apr 30 |
|
| Test-retest reliability of the unified Parkinson's disease rating scale in patients with early Parkinson's disease: results from a multicenter clinical trial. | 2002 Jul |
|
| An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic bcl-2 in human dopaminergic SH-SY5Y cells. | 2002 Jun 28 |
|
| Mitochondria determine the survival and death in apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, and neuroprotection by propargylamines. | 2002 May |
|
| Involvement of MAP kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline. | 2002 Oct |
|
| Neuroprotection by propargylamines in Parkinson's disease: suppression of apoptosis and induction of prosurvival genes. | 2002 Sep-Oct |
|
| Pharmacological comparison between the actions of methamphetamine and 1-aminoindan stereoisomers on sympathetic nervous function in rat vas deferens. | 2003 Jul 11 |
|
| Amyloid processing and signal transduction properties of antiparkinson-antialzheimer neuroprotective drugs rasagiline and TV3326. | 2003 May |
|
| 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 |
|
| Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity. | 2003 Nov 17 |
|
| A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. | 2004 Apr |
|
| Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients. | 2004 Aug |
|
| Clinical applications of MAO-inhibitors. | 2004 Aug |
|
| Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease? | 2004 Jan |
|
| Drugs in development for Parkinson's disease. | 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 |
|
| N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor. | 2004 May |
|
| Cardiovascular activity of rasagiline, a selective and potent inhibitor of mitochondrial monoamine oxidase B: comparison with selegiline. | 2004 Oct |
|
| [The early therapy challenge]. | 2005 |
|
| Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy. | 2005 |
|
| Rasagiline. | 2005 |
|
| Novel neuroprotective mechanism of action of rasagiline is associated with its propargyl moiety: interaction of Bcl-2 family members with PKC pathway. | 2005 Aug |
|
| Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. | 2005 Aug |
|
| [Rasagiline. A new monoamine oxidase b inhibitor for Parkinson treatment]. | 2005 Jul |
|
| Present and future drug treatment for Parkinson's disease. | 2005 Nov |
|
| Novel potential neuroprotective agents with both iron chelating and amino acid-based derivatives targeting central nervous system neurons. | 2005 Nov 25 |
|
| In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET. | 2005 Oct |
|
| The neurochemical and behavioral effects of the novel cholinesterase-monoamine oxidase inhibitor, ladostigil, in response to L-dopa and L-tryptophan, in rats. | 2005 Oct |
|
| [Rasagiline in motor fluctuations]. | 2005 Sep |
|
| Cost-utility model of rasagiline in the treatment of advanced Parkinson's disease in Finland. | 2006 Apr |
|
| Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. | 2006 Apr 11 |
|
| Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's disease. | 2006 Feb |
|
| Rasagiline -- is there a place for this drug in managing Parkinson's disease? | 2006 Feb |
|
| Drugs in development for Parkinson's disease: an update. | 2006 Jan |
|
| Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness. | 2006 Jan |
|
| Rasagiline improves quality of life in patients with early Parkinson's disease. | 2006 May |
|
| Rasagiline: A second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease. | 2006 May 15 |
|
| Rationale for considering that propargylamines might be neuroprotective in Parkinson's disease. | 2006 May 23 |
|
| Safety of rasagiline in elderly patients with Parkinson disease. | 2006 May 9 |
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
Edited
Fri Dec 15 15:56:31 GMT 2023
by
admin
on
Fri Dec 15 15:56:31 GMT 2023
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| Record UNII |
LH8C2JI290
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| Record Status |
Validated (UNII)
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| Record Version |
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NCI_THESAURUS |
C667
Created by
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EMA ASSESSMENT REPORTS |
AZILECT (AUTHORIZED: PARKINSON DISEASE)
Created by
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NCI_THESAURUS |
C38149
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admin on Fri Dec 15 15:56:31 GMT 2023 , Edited by admin on Fri Dec 15 15:56:31 GMT 2023
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EMA ASSESSMENT REPORTS |
RASAGLINE RATIOPHARM (AUTHORIZED: PARKINSON DISEASE)
Created by
admin on Fri Dec 15 15:56:31 GMT 2023 , Edited by admin on Fri Dec 15 15:56:31 GMT 2023
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LH8C2JI290
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LH8C2JI290
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m9504
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HH-53
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C66511
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DTXSID8047848
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SUB21334
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3052775
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CHEMBL887
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100000091287
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DBSALT001384
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577300
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
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