Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C12H13N.ClH |
| Molecular Weight | 207.699 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.C#CCN[C@@H]1CCC2=CC=CC=C12
InChI
InChIKey=SROCRRNUGWYRHJ-UTONKHPSSA-N
InChI=1S/C12H13N.ClH/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;/h1,3-6,12-13H,7-9H2;1H/t12-;/m1./s1
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 |
|---|---|---|
| Recent approaches to novel anti-Alzheimer therapy. | 2004 |
|
| [Are there innovations in the treatment of Parkinson's disease?]. | 2004 Nov 3 |
|
| Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. | 2004 Oct |
|
| Novel bifunctional drugs targeting monoamine oxidase inhibition and iron chelation as an approach to neuroprotection in Parkinson's disease and other neurodegenerative diseases. | 2004 Oct |
|
| 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 |
|
| [The early therapy challenge]. | 2005 |
|
| Alternatives to levodopa in the initial treatment of early Parkinson's disease. | 2005 |
|
| Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy. | 2005 |
|
| Rasagiline. | 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 |
|
| Novel neuroprotective mechanism of action of rasagiline is associated with its propargyl moiety: interaction of Bcl-2 family members with PKC pathway. | 2005 Aug |
|
| Rasagiline. | 2005 Aug |
|
| Reexamination of the TEMPO Study. | 2005 Aug |
|
| 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 |
|
| Binding of rasagiline-related inhibitors to human monoamine oxidases: a kinetic and crystallographic analysis. | 2005 Dec 29 |
|
| A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. | 2005 Feb |
|
| 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 |
|
| Movement disorders: understanding clinical trials. | 2005 Jan |
|
| Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. | 2005 Jan 1-15 |
|
| [Rasagiline. A new monoamine oxidase b inhibitor for Parkinson treatment]. | 2005 Jul |
|
| Parkinson's disease. Diagnosis and the initiation of therapy. | 2005 Jun |
|
| Neuropharmacological, neuroprotective and amyloid precursor processing properties of selective MAO-B inhibitor antiparkinsonian drug, rasagiline. | 2005 Jun |
|
| Characterization of the neuroprotective activity of rasagiline in cerebellar granule cells. | 2005 Mar |
|
| 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 |
|
| Rasagiline for motor complications in Parkinson's disease. | 2005 Mar 12-18 |
|
| Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004. | 2005 May |
|
| Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors. | 2005 Nov |
|
| Present and future drug treatment for Parkinson's disease. | 2005 Nov |
|
| Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine. | 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 |
|
| Rasagiline in the pharmacotherapy of Parkinson's disease--a review. | 2005 Oct |
|
| Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. | 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 |
|
| Neuroprotection by rasagiline: a new therapeutic approach to Parkinson's disease? | 2005 Summer |
|
| 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 |
|
| N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial membrane and induction of anti-apoptotic Bcl-2. | 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.
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9794292
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136236-50-5
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2V1ZE3067R
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C031967
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ACTIVE MOIETY
SUBSTANCE RECORD
