QuickView for Rasagiline (compound)

Summary
General Info

PubChem

PubChem Compound 122316

Name:	rasagiline
PubChem Compound ID:	122316
Molecular formula:	C₁₂H₁₃N
Molecular weight:	171.238 g/mol
Synonyms:	Agn-1135; Rasagiline; Agn 1135; 1H-Inden-1-amine, 2,3-dihydro-N-2-propynyl-; 1875-50-9; N-2-Propynyl-1-indanamine; 2,3-Dihydro-N-2-propynyl-1H-inden-1-amine

DrugBank

Identification

Name:	rasagiline
Name (isomeric):	DB01367
Drug Type:	small molecule
Synonyms:	RAS
Brand:	Azilect
Category:	Monoamine Oxidase Inhibitors, Neuroprotective Agents
CAS number:	136236-51-6

Pharmacology

Indication:	For the treatment of the signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa.
Pharmacology:	Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body i... show more » Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications. show less «
Mechanism of Action:	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. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in mo... show more » 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. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in models of dopaminergic motor dysfunction. show less «
Absorption:	Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.
Protein binding:	Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/ml.
Biotransformation:	Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism.
Route of elimination:	Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted as unchanged drug in urine.
Half Life:	Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B.
Toxicity:	Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol and caffeine.

Drug interaction:

Methamphetamine	Possible hypertensive crisis
Procaterol	Increased arterial pressure
Ephedrine	Increased arterial pressure
Imipramine	Possibility of severe adverse effects
Clomipramine	Possibility of severe adverse effects

Methamphetamine	Possible hypertensive crisis
Procaterol	Increased arterial pressure
Ephedrine	Increased arterial pressure
Imipramine	Possibility of severe adverse effects
Clomipramine	Possibility of severe adverse effects
Tranylcypromine	Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Citalopram	Possible severe adverse reaction with this combination
Phentermine	Possible hypertensive crisis
Amphetamine	Possible hypertensive crisis
Ephedra	Increased arterial pressure
Phenylephrine	Increased arterial pressure
Amitriptyline	Possibility of severe adverse effects
Brimonidine	MAO Inhibitors like rasagiline may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.
Mazindol	Possible hypertensive crisis
Amoxapine	Possibility of severe adverse effects
Dopamine	Increased arterial pressure
Escitalopram	Possible severe adverse reaction with this combination
Paroxetine	Possible severe adverse reaction with this combination
Duloxetine	Possible severe adverse reaction with this combination
Trimipramine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Tetrabenazine	Tetrabenazine may increase the adverse/toxic effects of Rasagiline. Concomitant therapy is contraindicated.
Buspirone	Possible blood pressure elevation
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dobutamine	Increased arterial pressure
Mirtazapine	Possible severe adverse reaction with this combination
Norepinephrine	Increased arterial pressure
Phenylpropanolamine	Increased arterial pressure
Dextromethorphan	Possible severe adverse reaction
Tramadol	Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, rasagiline.
Pirbuterol	Increased arterial pressure
Desipramine	Possibility of severe adverse effects
Dextroamphetamine	Possible hypertensive crisis
Tolcapone	Tolcapone and Rasagiline decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
Sertraline	Possible severe adverse reaction with this combination
Pseudoephedrine	Increased arterial pressure
Phendimetrazine	Possible hypertensive crisis
Cyclobenzaprine	Increased risk of toxicity with this association
Fluoxetine	Possible severe adverse reaction with this combination
Benzphetamine	MAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.
Protriptyline	Possibility of severe adverse effects
Nefazodone	Possible severe adverse reaction with this combination
Atomoxetine	Possible severe adverse reaction with this combination
Bupropion	Possible severe adverse reaction with this combination
Isoproterenol	Increased arterial pressure
Doxepin	Possibility of severe adverse effects
Fenoterol	Increased arterial pressure
Sibutramine	Possible serotoninergic syndrome with this combination
Epinephrine	Increased arterial pressure
Methylphenidate	Possible hypertensive crisis with this combination.
Altretamine	Risk of severe hypotension
Salbutamol	Increased arterial pressure
Buprenorphine	Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like rasagiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Ciprofloxacin	Ciprofloxacin, a strong CYP1A2 inhibitor, may decrease the metabolism of rasagiline. Monitor for changes in the therapeutic and adverse effects of rasagiline if ciprofloxacin is initiated or discontinued.
Phenmetrazine	Possible hypertensive crisis
St. John's Wort	Increased risk of toxicity with this association
Terbutaline	Increased arterial pressure
Meperidine	Increased risk of serotonin syndrome. Concomitant use should be avoided.
Fluvoxamine	Possible severe adverse reaction with this combination
Midodrine	Risk of hypertensive crisis.
Zolmitriptan	The MAO inhibitor, rasagiline, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing rasagiline are contraindicated.
Orciprenaline	Increased arterial pressure
Metaraminol	Increased arterial pressure
Methoxamine	Increased arterial pressure
Bezafibrate	MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) rasagiline.
Nortriptyline	Possibility of severe adverse effects
Desvenlafaxine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Diethylpropion	Possible hypertensive crisis
Dexfenfluramine	Possible hypertensive crisis
Venlafaxine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Fenfluramine	Possible hypertensive crisis
Mephentermine	Increased arterial pressure

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Targets

Amine oxidase [flavin-containing] B

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine

UniProt ID:

P27338

Gene:

MAOB

Actions:

inhibitor

References:

Naoi M, Maruyama W: Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease. Expert Rev Neurother. 2009 Aug;9(8):1233-50.
View Article

Uzun M, Alp R, Uzlu E, Alp S, Citil M, Topcu B, Erdogan HM: Investigation of oral selegiline and rasagiline administration on QT interval in conscious rabbits. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):95-8.
View Article

Youdim MB, Weinstock M: Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol. 2001 Dec;21(6):555-73.
View Article

Chau KY, Cooper JM, Schapira AH: Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. Neurochem Int. 2010 Jul 17.
View Article

Weinreb O, Amit T, Bar-Am O, Youdim MB: RASAGILINE; A NOVEL ANTI-PARKINSONIAN MONOAMINE OXIDASE-B INHIBITOR WITH NEUROPROTECTIVE ACTIVITY. Prog Neurobiol. 2010 Jun 19.
View Article

Youdim MB, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T: Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res. 2005 Jan 1-15;79(1-2):172-9.
View Article

Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinson's disease. Clin Interv Aging. 2010 May 25;5:149-56.
View Article

Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clin Ther. 2007 Sep;29(9):1825-49.
View Article

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

Apoptosis regulator Bcl-2

Enzymes

Cytochrome P450 1A2