药品详细

Rasagiline(雷沙吉兰)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

雷沙吉兰

英文名

Rasagiline

分子式

C₁₂H₁₃N

化学名

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

分子量

Average: 171.2383
Monoisotopic: 171.104799421

CAS号

136236-51-6

ATC分类

N04B 未知

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

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.

生产厂家

Teva neuroscience inc

封装厂家

参考

Synthesis Reference

Not Available

General Reference

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. Pubmed
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. Pubmed
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. Pubmed

剂型

规格

化合物类型

Type	small molecule

Classes

Indanes
Phenylpropylamines

Substructures

Indanes
Alkynes
Aliphatic and Aryl Amines
Benzene and Derivatives
Aromatic compounds
Phenylpropylamines

适应症

药理

Indication	For the treatment of the signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa.
Pharmacodynamics	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.
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 models of dopaminergic motor dysfunction.
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.
Clearance	Not Available
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
Pathways	Not Available

理化性质

Properties

State

solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	2.49e-02 g/l	ALOGPS
logP	2.26	ALOGPS
logP	2.3	ChemAxon
logS	-3.8	ALOGPS
pKa (strongest basic)	8.69	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	1	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	12.03	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	54.47	ChemAxon
polarizability	20.25	ChemAxon

药物相互作用

Drug	Interaction
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
Isoproterenol	Increased arterial pressure
Mazindol	Possible hypertensive crisis
Meperidine	Increased risk of serotonin syndrome. Concomitant use should be avoided.
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
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.

食物相互作用

Avoid alcohol and caffeine.

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