Rasagiline

Các tên gọi khác (4 ) :

(1R)-N-Propargylindan-1-amine
(R)-Indan-1-yl-prop-2-ynyl-amine
(R)-N-2-Propynyl-1-indanamine
RAS

neuroprotective agents, monoamine oxidase inhibitors

Thuốc Gốc

Small Molecule

CAS: 136236-51-6

ATC: N04BD02

ĐG : Murfreesboro Pharmaceutical Nursing Supply , http://www.unitdosesupply.com

CTHH: C₁₂H₁₃N

PTK: 171.2383

Rasagiline is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₂H₁₃N

Phân tử khối

171.2383

Monoisotopic mass

171.104799421

InChI

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

InChI Key

InChIKey=RUOKEQAAGRXIBM-GFCCVEGCSA-N

IUPAC Name

(1R)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine

Traditional IUPAC Name

rasagiline

SMILES

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

Độ hòa tan

2.49e-02 g/l

logP

2.3

logS

-3.8

pKa (Strongest Basic)

8.69

PSA

12.03 Å²

Refractivity

54.47 m³·mol^-1

Polarizability

20.25 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : Rasagiline is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases. 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.

Dược Động Học :

▧ Absorption :
Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.
▧ Volume of Distribution :
* 87 L
▧ 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.
▧ Metabolism :
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.

Độc Tính : 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.

Chỉ Định : For the treatment of the signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa.

Tương Tác Thuốc :

Altretamine Risk of severe hypotension
Amitriptyline Possibility of severe adverse effects
Amoxapine Possibility of severe adverse effects
Amphetamine Possible hypertensive crisis
Atomoxetine 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.
Bezafibrate MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) rasagiline.
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.
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.
Bupropion Possible severe adverse reaction with this combination
Buspirone Possible blood pressure elevation
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.
Citalopram Possible severe adverse reaction with this combination
Clomipramine Possibility of severe adverse effects
Cyclobenzaprine Increased risk of toxicity with this association
Desipramine 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.
Dexfenfluramine Possible hypertensive crisis
Dextroamphetamine Possible hypertensive crisis
Dextromethorphan Possible severe adverse reaction
Diethylpropion Possible hypertensive crisis
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Doxepin Possibility of severe adverse effects
Duloxetine Possible severe adverse reaction with this combination
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Escitalopram Possible severe adverse reaction with this combination
Fenfluramine Possible hypertensive crisis
Fenoterol Increased arterial pressure
Fluoxetine Possible severe adverse reaction with this combination
Fluvoxamine Possible severe adverse reaction with this combination
Imipramine Possibility of severe adverse effects
Isoprenaline Increased arterial pressure
Mazindol Possible hypertensive crisis
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methamphetamine Possible hypertensive crisis
Methoxamine Increased arterial pressure
Methylphenidate Possible hypertensive crisis with this combination.
Midodrine Risk of hypertensive crisis.
Milnacipran Increase serotonin levels. Combination therapy is contraindicated.
Mirtazapine Possible severe adverse reaction with this combination
Nefazodone Possible severe adverse reaction with this combination
Norepinephrine Increased arterial pressure
Nortriptyline Possibility of severe adverse effects
Orciprenaline Increased arterial pressure
Paroxetine Possible severe adverse reaction with this combination
Pethidine Increased risk of serotonin syndrome. Concomitant use should be avoided.
Phendimetrazine Possible hypertensive crisis
Phenmetrazine Possible hypertensive crisis
Phentermine Possible hypertensive crisis
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Pirbuterol Increased arterial pressure
Procaterol Increased arterial pressure
Protriptyline Possibility of severe adverse effects
Pseudoephedrine Increased arterial pressure
Salbutamol Increased arterial pressure
Sertraline Possible severe adverse reaction with this combination
Sibutramine Possible serotoninergic syndrome with this combination
St. John's Wort Increased risk of toxicity with this association
Tapentadol Increases the toxicity of tapentadol by unknown mechanism. Discontinue rasagiline at least 14 days prior to tapentadol administration.
Terbutaline Increased arterial pressure
Tetrabenazine Tetrabenazine may increase the adverse/toxic effects of Rasagiline. Concomitant therapy is contraindicated.
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.
Tramadol Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, rasagiline.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
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.
Venlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
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.

Liều Lượng & Cách Dùng : Tablet - Oral
Tablet - Oral - 0.5 mg
Tablet - Oral - 1 mg

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Azilect 0.5 mg tablet

Giá bán buôn : USD >12.11

Đơn vị tính : tablet
Biệt dược thương mại : Azilect 1 mg tablet

Giá bán buôn : USD >12.11

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Azilect

Đóng gói

Công ty : Murfreesboro Pharmaceutical Nursing Supply

Website : http://www.unitdosesupply.com
Công ty : Teva Pharmaceutical Industries Ltd.

Website : http://www.tevapharm.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01367

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3052776

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506045

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02562

ChemSpider

http://www.chemspider.com/Chemical-Structure.2314553.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=10989

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/68546-142-56

PharmGKB

http://www.pharmgkb.org/drug/PA164764584

Wikipedia

http://en.wikipedia.org/wiki/Rasagiline

RxList

http://www.rxlist.com/cgi/generic/azilect.htm

Drugs.com

http://www.drugs.com/cdi/rasagiline.html

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