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药品详细

Rizatriptan(利扎曲坦)

化学结构式图
中文名
利扎曲坦
英文名
Rizatriptan
分子式
C15H19N5
化学名
dimethyl({2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl})amine
分子量
Average: 269.3449
Monoisotopic: 269.164045633
CAS号
145202-66-0
ATC分类
N02C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Rizatriptan is a triptan drug used for the treatment of migraine headaches. It is a selective 5-hydroxytryptamine1 receptor subtype agonist.

生产厂家
  • Merck and co inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Wellington K, Plosker GL: Rizatriptan: an update of its use in the management of migraine. Drugs. 2002;62(10):1539-74. Pubmed
  2. Wellington K, Jarvis B: Spotlight on rizatriptan in migraine. CNS Drugs. 2002;16(10):715-20. Pubmed
  3. Ikemoto F, Toru T, Aijima H, Natsumeda Y: [Rizatriptan (Maxalt), a new entity of triptan for migraine: pharmacology and therapeutic relevance] Nippon Yakurigaku Zasshi. 2004 Apr;123(4):295-302. Pubmed
  4. Villalon CM, Centurion D, Valdivia LF, De Vries P, Saxena PR: An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210. Pubmed
  5. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Tryptamines and Derivatives
Substructures
  • Indoles and Indole Derivatives
  • Triazoles
  • Pyrroles
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Tryptamines and Derivatives
  • Cyanamides
适应症
药理
Indication For treatment of acute migraine attacks with or without aura.
Pharmacodynamics Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Rizatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Rizatriptan in humans.
Mechanism of action Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.
Absorption Rapid following oral administration. Bioavailability is 45%. Food has no effect on the bioavailability of rizatriptan. However, administering rizatriptan with food will delay by 1 hour the time to reach peak plasma concentration. The rate of absorption is not affected by the presence of a migraine attack.
Volume of distribution
  • 140 L [male]
  • 110 L [female]
Protein binding 14%
Metabolism
Rizatriptan is metabolized by monoamine oxidase A isoenzyme (MAO-A) to an inactive indole acetic acid metabolite. In addition, several other inactive metabolites are formed. An active metabolite, N-monodesmethyl-rizatriptan, with pharmacological activity similar to that of the parent compound has been identified in small concentrations (14%) in the plasma.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Rizatriptan
    		N-monodesmethyl-rizatriptan Details
    Route of elimination Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism.
    Half life 2-3 hours
    Clearance Not Available
    Toxicity Symptoms of overdose include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 178-180 °C Not Available
    water solubility 42 mg/mL (for free base) Not Available
    logP 1.4 Not Available
    Predicted Properties
    Property Value Source
    water solubility 3.38e-01 g/l ALOGPS
    logP 1.67 ALOGPS
    logP 1.77 ChemAxon
    logS -2.9 ALOGPS
    pKa (strongest acidic) 17.24 ChemAxon
    pKa (strongest basic) 9.56 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 49.74 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 93.13 ChemAxon
    polarizability 30 ChemAxon
    药物相互作用
    Drug Interaction
    Citalopram Increased risk of CNS adverse effects
    Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Dihydroergotamine Possible severe and prolonged vasoconstriction
    Ergotamine Possible severe and prolonged vasoconstriction
    Escitalopram Increased risk of CNS adverse effects
    Fluoxetine Increased risk of CNS adverse effects
    Fluvoxamine Increased risk of CNS adverse effects
    Isocarboxazid The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
    Methysergide Possible severe and prolonged vasoconstriction
    Moclobemide The MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
    Nefazodone Increased risk of CNS adverse effects
    Paroxetine Increased risk of CNS adverse effects
    Phenelzine The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
    Propranolol Propranolol increases the effect and toxicity of rizatriptan
    Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Tranylcypromine The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Rizatriptan. Risk of serotonin syndrome and Rizatriptan toxicity. Concomitant therapy should be avoided.
    Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Zolmitriptan Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and rizatriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
    食物相互作用
    Not Available

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